Diversity, Versatility and Leukaemia

Geoffrey Brown
College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK

Isidro Sanchez-Garcia
Senior Staff Researcher, IBMCC-CSIC/University of Salamanca, Salamanca, Spain

Series: Cancer Etiology, Diagnosis and Treatments
BISAC: MED062000

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The blood cell system has provided a model system that has been used by many researchers to investigate how a stem cell can give rise to a wide variety of mature cell types. The principles that emerged in developmental biology have been applied to the structure of tissues throughout the body. However, many of the principles have been challenged by recent findings, changing the way we view blood cell development. In turn, this has impacted our understanding of the origin and nature of leukaemia, as well as cancer in general. Like the development of any body tissue, cancer is an organised and hierarchical tissue with its own identity. A new viewpoint is that the mutations that give rise to cancer re-programme cancer cells to their own abnormal pattern of tissue development. Understanding how the hierarchy of tumour identity differs from that of normal tissue provides important new avenues to the development of new treatments for cancer. No doubt further refinement to our understanding of normal and cancer cells will continue for many years to come. Even so, we appear to be moving towards an exciting prospect of providing the key to unlocking the long standing mystery of primary cellular events that undermine and distort our normal cells and give rise to the disease of cancer. The importance of this is the prospect of developing new treatments for cancer. In particular, the distorted behaviour of cancer cells might be reversible so that they can be restored to their normal state. Diversity, Versatility and Leukaemia examines how normal and cancer cells are inextricably linked, and focuses on the changes to how we view the development of normal cells and the subversion of this process in cancer.
(Imprint: Nova Biomedical)

Preface

Short Abstract

Acknowledgments

Chapter 1. The Diversity of Blood Cells

Chapter 2. The Conventional Viewpoint to Haematopoiesis

Chapter 3. Revision to the Model of Haematopoiesis

Chapter 4. Classifying the Various Leukaemias/Haematopoietic Cancers

Chapter 5. Leukaemia/Haematopoietic Cancer-initiating Cellular Events

Chapter 6. Leukaemia/Haematopoietic Cancers and Lineage Commitment

Chapter 7. The Prospect of New Treatments for Leukaemia and Other Cancers

Authors' Contact Information

Index

“Based largely on technological advances allowing single cell transcriptomic and proteomic analyses, our accepted concepts of tumour biology are undergoing revolutionary changes. This book, written by two world leaders in experimental haematology, provides an excellent comprehensive account of how our views on tumours of white blood cells (leukaemias) have to be modified.” - Professor Rhodri Ceredig, MB, ChB, PhD, FRCPath, Director, National Centre for Biomedical Engineering Science, Galway, Ireland

“Our knowledge on biology of hematopoietic progenitors and leukemogenesis is constantly evolving, changing our concepts on these processes. In this book, two experts in the field, provide comprehensive summary on new discoveries in hematopoiesis and leukemogenesis, emphasizing versatile functions of HSCs and HPCs as well as cancer stem cells, in these processes and potential application of new knowledge on therapy of leukemia.” - Izidore S. Lossos M.D., Director, Lymphoma Program, University of Miami, Sylvester Comprehensive Cancer Center, Miami, Florida

“This excellent book provides a critical review of current progress towards a better understanding of the cellular and molecular mechanisms of normal bone marrow function and the development of various forms of leukaemia. While stressing the complexity of this rapidly moving field of research it offers valuable insights into its future therapeutic possibilities. It will be of great value, not only to hematologists, but to workers in any form of malignant disease.” - Professor Sir David Weatherall, KBE FRS FMedSci, The Weatherall Institute of Molecular Medicine, University of Oxford

Chapter 1

[1] Huxley, T. H., Lessons in Elementary Physiology. (1871). Pub. MacMillan and Co., London and New York.
[2] Gibson, R. J. H., A textbook of elementary biology. (1889). Pub. Longmans, Green, and Co., London and New York.
[3] Schafer, E. A., The Essentials of Histology. (1892). Pub. Longmans, Green and Co., London.
[4] Woronzoff-Dashkoff, K. P., The Ehrlich-Chenzinsky-Plehn-Malachowski-Romanowsky-Nocht-Jenner-May-Grünw ald-Leishman-Reuter-Wright-Giemsa-Lillie-Roe-Wilcox stain. The mystery unfolds. Clin. Lab. Med. 1993. 13: 759-771.
[5] Houwen, B., Blood film preparation and staining procedures. Clin. Lab. Med. 2002. 22: 1-14.
[6] Ziegler-Heitbrock, L. and Hofer, T. P., Toward a refined definition of monocyte subsets. Front. Immunol. 2013. 4: Article 23.
[7] Naik, S. H., Demystifying the development of dendritic cells, a little. Immunol. Cell Biol. 2008. 86: 439-452.
[8] Artis, D. and Splits, H., The biology of innate lymphoid cells. Nature 2015. 517: 293-301.
[9] den Haan, J. M., Arens, R. and van Zelm, M. C., The activation of the adaptive immune system: cros-talk between antigen-presenting cells, T cells and B cells. Immunol. Lett. 2014. 162: 103-112.
[10] Shah, D. K. and Zuniga-Pflucker, J. C., An overview of the intrathymic intracacies of T cell development. J. Immunol. 2014. 192: 4017-4023.
[11] Sun, B. and Zhang, Y., Overview of orchestration of CD4+ T cell subsets in immune responses. Adv. Exp. Med. Biol. 2014. 841: 1-13.
[12] Kawamoto, H. and Katsura, Y., A new paradigm for hematopoietic cell lineages: revision of the classical concept of the myeloid-lymphoid dichotomy. Trends Immunol. 2009. 30: 193–200.
[13] Porritt, H. E., Rumfelt, L. L., Tabrizifard, S., Schmitt, T.M., Zúñiga-Pflücker, J.C. and Petrie, H.T., Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 2004. 20: 735–745.
[14] Balciunaite, G., Ceredig, R. and Rolink, A. G., The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential. Blood 2005. 105: 1930–1936.

Chapter 2

[1] Till, J. E. and McCulloch, E. A., A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 1961. 14: 215-222.
[2] Rumman, M., Dhawan, J. and Kassem, M., Concise review: Quiescence in adult stem cells: biological significance and relevance to tissue regeneration. Stem Cells 2015. 33: 2903-2912.
[3] Bendall, L. J. and Bradstock, K. F., G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilising agent. Cytokine Growth Factor Rev. 2014. 25: 355-367.
[4] Spangrude, G. J., Heimfeld, S. and Weissman I. L., Purification and characterisation of mouse hematopoietic stem cells. Science 1988. 241: 58-62.
[5] Osawa, M., Hanada, K., Hamada, H. and Nakauchi, H., Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996. 273: 242-245.
[6] Spangrude, G. J., Brooks, D. M. and Tumas, D. B., Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells; in vivo expansion of stem cell phenotype but not function. Blood 1995. 85: 1006-1016.
[7] Christensen, J. L. and Weissman, I. L., Flk-2 is a marker of hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc. Natl. Acad. Sci. USA 2001. 98:14541-14546.
[8] Yang, L., Bryder, D., Adolfsson, J., Nygren, J., Månsson, R., Sigvardsson, M. and Jacobsen, S.E., Identification of Lin(-)Sca(+)kit(+)Flt3-short term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood 2005. 105: 2717-2723.
[9] Oguro, H., Ding, L. and Morrison, S. J., SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell 2013. 13: 102-116.
[10] Boulais, P. E. and Frenette, P. S., Making sense of hematopoietic stem cell niches. Blood 2015. 125: 2621-2629.
[11] Gottens, B., Regulatory network control of blood stem cells. Blood 2015. 125: 2614-2620.
[12] Bradley, T. R. and Metcalf, D., The growth of mouse bone marrow cells in vitro. Aust. J. Exp. Biol. 1966. 44: 287-299.
[13] Metcalf, D., The Florey Lecture The colony-stimulating factors: discovery to clinical use. Philos. Trans. R. Soc. Lond. B Biol. Sci. 1991. 333: 147-173.
[14] Weissman, I. L., Anderson, D. and Cage, F., Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiation. Ann. Rev. Cell. Dev. Biol. 2001. 17: 387-403.
[15] Laurent, J., Bosco, N., Marche, P. N. and Ceredig, R., New insights to the proliferation and differentiation of early mouse thymocytes. Int. Immunol. 2004. 16: 1069-1080.
[16] Dexter, T. M., Haematopoiesis in long-term bone marrow cultures. A review. Acta Haematol. 1979. 62: 299-305.
[17] Whitlock, C. A. and Witte, O. N., Long-term culture of B lymphocytes and their precursors from muring bone marrow. Proc. Natl. Acad. Sci. USA 1982. 79: 3608-3612.
[18] Kondo, M., Weissman, I. L. and Akashi, K., Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 1997. 91: 661-672.
[19] Akashi, K., Traver, D., Miyamoto, T. and Weissman, I. L., A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 2000. 404: 193-197.
[20] Holtzer, H., Stem cell concepts: comments and replies. Differentiation 1979. 14: 33-40.
[21] Sun, J., Ramos, A., Chapman, B., Johnnidis, J.B., Le, L., Ho, Y.J., Klein, A., Hofmann, O. and Camargo, F.D., Clonal dynamics of native haematopoiesis. Nature 2014. 514: 322–327.
[22] Ceredig, R., Rolink, A. and Brown, G., Models of haematopoiesis: seeing the wood for the trees. Nat. Rev. Immunol. 2009. 9:293-300.
[23] Katsura, Y., Redefinition of lymphoid progenitors. Nat. Rev. Immunol. 2002. 2: 127–132.
[24] Lai, A. Y. and Kondo, M., Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. J. Exp. Med. 2006. 203: 1867–1873.
[25] Ye, M. and Graf, T., Early decisions in lymphoid development. Curr. Opin. Immunol. 2007. 19, 123–128.
[26] Suda, T., Suda, J. and Ogawa M., Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. Proc. Natl. Acad. Sci. U.S.A.1984. 81: 2520–2524.
[27] Hu, M., Krause, D., Greaves, M., Sharkis, S., Dexter, M., Heyworth, C. and Enver, T., Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev. 1997. 11: 774–785.
[28] Cross, M. A and Enver, T., The lineage commitment of haemopoietic progenitor cells. Curr. Opin. Genet. Dev. 1997. 7: 609–613.
[29] Enver, T. and Greaves, M., Loops, lineage, and leukemia. Cell 1998. 94: 9–12.
[30] Kawamoto, H. and Katsura, Y., A new paradigm for hematopoietic cell lineages: revision of the classical concept of the myeloid-lymphoid dichotomy. Trends Immunol. 2009. 30: 193–200.

Chapter 3

[1] Graf, T., Immunology: Blood cells redrawn Nature 2008. 452: 702-703.
[2] Boyd, A. W. and Schrader, J. W., Nature 1982. 297: 691-693.
[3] Davidson, W.F., Pierce, J.H., Rudikoff, S. and Morse, H.C. 3rd., Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. J. Exp. Med. 1988. 168, 389–407.
[4] Tanaka, T., Wu, G.E. and Paige, C.J., Characterization of the B cell-macrophage lineage transition in 70Z/3 cells. Eur. J. Immunol. 1994. 24, 1544–1548.
[5] Borzillo, G.V., Ashmun, R. A. and Sherr, C. J., Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes. Mol. Cell. Biol. 1990. 10: 2703-2714.
[6] Klinken, S. P., Alexander, W.S. and Adams, J. M., Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages. Cell 1988. 53: 857-867.
[7] Fisher, A. G., Burdet, C., Bunce, C., Merkenschlager, M. and Ceredig, R., Lymphoproliferative disorders in IL-7 transgenic mice: expansion of immature B cells which retain macrophage potential. Int. Immunol. 1995.7: 415-423.
[8] Wong, A. K‑Y., Bunce, C. M., Lord, J. M., Salt, J. and Brown, G., Evidence that precursor cells of monocytes and B lymphocytes are closely related. Expt. Hematol. 1989. 17: 968‑973.
[9] Cumano, A., Paige, C. J., Iscove, N. N. and Brady, G., Bipotential precursors of B cells and macrophages in murine fetal liver. Nature 1992. 356: 612–615.
[10] Montecino-Rodriguez, E., Leathers, H. and Dorshkind, K., Bipotential Bmacrophage progenitors are present in adult bone marrow. Nat. Immunol. 2001. 2: 83–88.
[11] Li, J., Barreda, D.R,, Zhang, Y.A., Boshra, H., Gelman, A.E., Lapatra, S., Tort, L. and Sunyer, J.O., B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities. Nat. Immunol. 2006. 7, 1116–1124.
[12] Balciunaite, G., Ceredig, R., Massa, S. and Rolink, A. G., A B220+ CD117+ CD19- hematopoietic progenitor with potent lymphoid and myeloid developmental potential. Eur. J. Immunol. 2005. 35: 2019-2030.
[13] Nutt, S. L., Heavey, B., Rolink, A. G. and Busslinger, M., Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 1999. 401: 556-562.
[14] Rolink, A. G., Nutt, S.L., Melchers, F. and Busslinger, M., Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature 1999. 401: 603-606.
[15] Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C.T., Bryder, D., Yang, L., Borge, O.J., Thoren, L.A., Anderson, K., Sitnicka, E., Sasaki, Y., Sigvardsson, M. and Jacobsen, S.E., Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 2005. 121: 295-306.
[16] Brown, G., Hughes, P. J., Ceredig, R. and Michell, R. H., Versatility and nuances of the architecture of haematopoiesis – Implications for the nature of leukaemia Leuk. Res. 2012. 36: 14-22.
[17] Challen, G. A., Boles, N. C., Chambers, S. M. and Goodell, M. A., Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1. Cell Stem Cell 2010. 6: 265-278.
[18] Morita, Y., Ema, H. and Nakauchi, H., Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 2010. 207: 1173-1182.
[19] Gekas, C. and Graf, T., CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age. Blood 2013. 121: 4463-4472.
[20] Shimazu, T., Iida, R., Zhang, Q., Welner, R. S., Medina, K. L., Alberola-Lla, J. and Kincade, P. W., CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential. Blood 2012. 119: 4889-4897.
[21] Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D. and Rossi, D. J., Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc. Natl. Acad. Sci. USA 2010. 107: 5465-5470.
[22] Sanjuan-Pla, A., Macaulay, I. C., Jensen, C. T., Woll, P. S., Luis, T. C., Mead, A., Moore, S., Carella, C., Matsuoka, S., Bouriez Jones, T., Chowdhury, O., Stenson, L., Lutteropp, M., Green, J. C., Facchini, R., Boukarabila, H., Grover, A., Gambardella, A., Thongjuea, S., Carrelha, J., Tarrant, P., Atkinson, D., Clark, S. A., Nerlov, C. and Jacobsen, S. E., Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature 2013. 502: 232-236.
[23] Notta, F., Zandi, S., Takayama, N., Dobson, S., Gan, G., Kaufmann, K. B., McLeod, J., Laurenti, E., Dunant, C. F., McPherson, J. D., Stein, L. D., Dror, Y. and Dick, J. E., Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science 2015. doi: 10.1126/science.aab2116.
[24] Mercier, F. E. and Scadden, D. T., Not all created equal: Lineage Hard-wiring in the production of blood. Cell 2015. 163: 1568-1570.
[25] Perie, L., Duffy, K. R., Kok, L., de Boer, R. J. and Schumacher, T. N., The branching point in erythro-myeloid differentiation. Cell 2015. 163: 1655-1662.
[26] Paul, F., Arkin, Y., Giladi, A., Jaitin, D.A., Kenigsberg, E., Keren-Shaul, H., Winter, D., Lara-Astiaso, D., Gury, M., Weiner, A., David, E., Cohen, N., Lauridsen, F.K., Haas, S., Schlitzer, A., Mildner, A., Ginhoux, F., Jung, S., Trumpp, A., Porse, B. T., Tanay, A. and Amit, I., Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell 2015. 163: 1663-1677.
[27] Ye, M. and Graf, T., Early decisions in lymphoid development. Curr. Opin. Immunol. 2007. 19: 123-128.
[28] Katsura, Y., Redefinition of lymphoid progenitors. Nat. Rev. Immunol. 2002. 2: 127-132.
[29] Ishikawa, F., Niiro, H., Lino, T., Yoshida, S., Saito, N., Onohara, S., Miyamoto, T., Minagawa, H., Fujii, S., Shultz, L.D., Harada, M. and Akashi, K., The developmental programme of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways. Blood 2007. 110: 3591–3660.
[30] Brown, G., Hughes, P. J., Michell, R. H. and Ceredig, R., The versatility of haematopoietic stem cells: implications for leukaemia. Crit. Rev. Clin. Lab. Sci. 2010. 47: 171–180.
[31] Braunstein, M., Rajkumar, P., Claus, C. L., Vaccarelli, G., Moore, A. J., Wang, D. and Anderson, M. K., HEBAlt enhances the T-cell potential of myeloid biased precursors. Int. Immunol. 2010. 22: 963–972.
[32] Benne, C., Lelievre, J. D., Balbo, M., Henry, A., Sakano, S. and Levy, Y., Notch increases T/NK potential of human hematopoietic progenitors and inhibits B cell differentiation at the pro-B stage. Stem Cells 2009. 27: 1676–1685.
[33] Fogg, D. K., Sibon, C., Miled, C., Jung, S., Aucouturier, P., Littman. D. R., Cumano, A. and Geissmann, F., A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 2006. 311: 83–87.
[34] Shankland, M., Differentiation of the O and P cell lines in the embryo of the leech. II. Genealogical relationship of descendant pattern elements in alternative developmental pathways. Dev. Biol. 1987. 123: 97–107.
[35] Porritt, H. E., Rumfelt, L. L., Tabrizifard, S., Schmitt, T.M., Zúñiga-Pflücker, J.C. and Petrie, H.T., Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 2004. 20: 735–745.
[36] Benz, C. and Bleul, C. C., A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision. J. Exp. Med. 2005. 202: 21–31.
[37] Balciunaite, G., Ceredig, R. and Rolink, A. G., The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential. Blood 2005. 105: 1930–1936.
[38] Ceredig, R., Rolink, A. G. and Brown G., Opinion – Models of haematopoiesis: seeing the wood from the trees. Nat. Rev. Immunol. 2009. 9: 293-300.
[39] Brown, G. and Ceredig, R., lineage determination in haematopoiesis: Quo vadis. Trends Immunol. 2009. 30: 465-466.
[40] Brown, G., Mooney, C. J., Servera, L. A., Von Muenchow, L., Toellner, K-M., Ceredig, R. and Rolink, A. G., Versatility of stem and progenitor cells and the instructive action of cytokines on haematopoiesis. Crit. Rev. Clin. Lab. Sci. 2015. 52: 168-179.
[41] Brown, G., Hughes, P. J., Michell, R. H. and Ceredig, R., The versatility of haematopoietic stem cells: implications for leukaemia. Crit. Rev. Clin. Lab. Sci. 2010. 47: 171-180.
[42] Lohmann, F. and Bieker, J. J., Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid development. Development 2008. 135: 2071-2082.
[43] Frontelo, P., Manwani, D., Galdass, M., Karsunky, H., Lohmann, F., Gallager, P. G. and Bieker, J. J., Novel role for EKLF in megakaryocyte lineage commitment. Blood 2007. 110: 3871-3880.
[44] Brown, G., Hughes, P. J., Michell, R. H., Rolink, A. G. and Ceredig, R., The sequential determination model of hematopoiesis. Trends Immunol. 2007. 28: 442-448.
[45] Sun, J., Ramos, A., Chapman B., Johnnidis, J. B., Le, L., Ho, Y-J., Klein, A., Hofmann, O. and Camargo, F. D., Clonal dynamics of native haematopoiesis. Nature 2014. 514: 322-327.
[46] Metcalf, D. Hematopoietic cytokines. Blood 2008. 111: 485-491.
[47] Robb, L. Cytokine receptors and hematopoietic differentiation. Oncogene 2007. 26: 6715-6723.
[48] Nakahata, T. and Ogawa, M,. Clonal origin of murine hemopoietic colonies with apparent restriction to granuclocyte-macrophage-megakaryocyte (GMM) differentiation. J Cell Physiol. 1982. 111: 239-246.
[49] Ogawa, M., Porter, P. N. and Nakahata, T., Renewal and commitment to differentiation of hemopoietic stem cells (an interpretive review). Blood 1983. 61: 823-829.
[50] Suda, T., Suda, J. and Ogawa, M., Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. Proc. Natl. Acad. Sci. USA 1984. 81: 2520-2524.
[51]. Enver, T., Heyworth, C. M. and Dexter, T. M., Do stem cells play dice? Blood 1998. 92: 348-351; discussion 52.
[52] Metcalf, D. and Burgess, A. W., Clonal analysis of progenitor cell commitment of granulocyte or macrophage production. J Cell Physiol 1982. 111: 275-283.
[53] Metcalf, D., Lineage commitment of hemopoietic progenitor cells in developing blast cell colonies: influence of colony-stimulating factors. Proc. Natl. Acad. Sci. USA 1991. 88: 11310-11314.
[54] Rieger, M. A., Hoppe, P. S., Smejkal, B. M., Eitelhuber, A. C. and Schroeder, T., Hematopoietic cytokines can instruct lineage choice. Science 2009. 325: 217-218.
[55] Mossadegh-Keller, N., Sarrazin, S., Kandalla, P. K., Espinosa, L., Stanley, E. R., Nutt, S. L., Moore, J. and Sieweke, M. H., M-CSF instructs myeloid lineage fate in single haematopoietic stem cells. Nature 2013. 497: 239-243.
[56] Grover, A., Mancini, E., Moore, S., Mead, A. J, Atkinson, D., Rasmussen, K. D., O’Carrol, D., Jacobsen, S. E. and Nerlove, C., Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate. J Exp Med 2014. 211:181-188.
[57] Lyman, S. D., James, L., Vanden Bos, T., de Vries, P., Brasel, K., Gliniak, B., Hollingsworth L. T., Picha, K. S., McKenna, H. J. and Splett, R. R., Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. Cell 1993. 75: 1157-1167.
[58] Rasko, J. E., Metcalf, D., Rossner, M. T., Begley, C. G. and Nicola, N. A., The flt3/flk-2 ligand: receptor distribution and action on murine haemopoietic cell survival and proliferation. Leukemia 1995. 9: 2058-2066.
[59] Adolfsson, J., Borge, O. J., Bryder, D., Theilgaard-Monch, K., Astrand-Grundstrom, I., Sitnicka, E., Sasaki, Y. and Jacobsen, S. E., Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 2001. 15: 659-669.
[60] Tsapogas, P., Swee, L. K., Nusser, A., Nuber, N., Kreuzaler, M., Capoferri, G., Rolink, H., Ceredig, R. and Rolink, A., In vivo evidence for an instructive role of fms-like tyrosine kinase-3 (FLT3) ligand in hematopoietic development. Haematologica 2014. 99: 638-646.
[61] Ceredig, R., Rauch, M., Balciunaite, G. and Rolink, A. G., Increasing Flt3L availability alters composition of a novel bone marrow lymphoid progenitor compartment. Blood 2006. 108: 1216-1222.
[62] Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K. And Weissman, I. L., Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature 2000. 407: 383-386.

Chapter 4

[1] Swerdlow, S. H., Campo, E., Harris, N. L., Jaffe, E. S., Pileri, S. A., Stein, H., Thiele, J. and Vardiman, J. W., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon 2008. 4th Edition ed. 2008.
[2] Bennett, J. M., Catovsky, D., Daniel, M. T., Flandrin, G., Galton, D. A., Gralnick, H. R. and Sultan C., Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. British J. Haematol., 1976. 33: 451-458.
[3] Porwit, A. and Bene, M. C., Acute leukemias of ambiguous origin. Am. J. Clin. Pathol. 2015. 144: 361-376.
[4] Grimwade, D., Walker, H., Oliver, F., Wheatley, K., Harrison, C., Harrison, G., Rees, J., Hann, I., Stevens, R., Burnett, A. and Goldstone A., The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998. 92: 2322-2333.
[5] Grimwade, D., The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia. Best practice & research. Clin. Haematol, 2001. 14: 497-529.
[6] Downing, J. R. and Shannon, K. M., Acute leukemia: a pediatric perspective. Cancer Cell 2002. 2: 437-445.
[7] Pui, C. H., Mullighan, C. G., Evans, W. E. and Relling, M. V., Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood 2012. 120: 1165-1174.
[8] Bea, S., Zettl, A., Wright, G., Salaverria, I., Jehn, P., Moreno, V., Burek, C., Ott, G., Puig, X., Yang, L., Lopez-Guillermo, A., Chan, W. C., Greiner, T. C., Weisenburger, D. D., Armitage, J. O., Gascoyne, R. D., Connors, J. M., Grogan, T. M., Braziel, R., Fisher, R. I., Smeland, E. B., Kvaloy, S., Holte, H., Delabie, J., Simon, R., Powell, J., Wilson, W. H., Jaffe, E. S., Montserrat, E., Muller-Hermelink, H. K., Staudt, L.M., Campo, E. and Rosenwald A., Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumour biology and improve gene-expression-based survival prediction. Blood 2005. 106: 3183-3190.
[9] Chen, W., Houldsworth, J., Olshen, A. B., Nanjangud, G., Chaganti, S., Venkatraman, E. S., Halaas, J., Teruya-Feldstein, J., Zelenetz, A. D. and Chaganti, R. S., Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas. Blood 2006. 107: 2477-2485.
[10] Tagawa, H., Suguro, M., Tsuzuki, S., Matsuo, K., Karnan, S., Ohshima, K., Okamoto, M., Morishima, Y., Nakamura, S. and Seto, M., Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma. Blood 2005. 106: 1770-1777.
[11] Alizadeh, A. A., Eisen, M. B., Davis, R. E., Ma, C., Lossos, I. S., Rosenwald, A., Boldrick, J. C., Sabet, H., Tran, T., Yu, X., Powell, J. I., Yang, L., Marti, G. E., Moore, T., Hudson, J. Jr., Lu, L., Lewis, D. B., Tibshirani, R., Sherlock, G., Chan, W. C., Greiner, T. C., Weisenburger, D. D., Armitage, J. O., Warnke, R., Levy, R., Wilson, W., Grever, M. R., Byrd, J. C., Botstein, D., Brown, P. O. and Staudt, L. M., Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000. 403: 503-511.
[12] Rosenwald, A., Wright, G., Leroy, K., Yu, X., Gaulard, P., Gascoyne, R. D., Chan, W. C., Zhao, T., Haioun, C., Greiner, T. C., Weisenburger, D. D., Lynch, J. C., Vose, J., Armitage, J. O., Smeland, E. B., Kvaloy, S., Holte, H., Delabie, J., Campo, E., Montserrat, E., Lopez-Guillermo, A., Ott, G., Muller-Hermelink, H. K., Connors, J. M., Braziel, R., Grogan, T. M., Fisher, R. I., Miller, T. P., LeBlanc, M., Chiorazzi, M., Zhao, H., Yang, L., Powell, J., Wilson, W. H., Jaffe, E. S., Simon, R., Klausner, R. D. and Staudt, L. M., Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J. Exp. Med. 2003. 198: 851-862.
[13] Rosenwald, A., Wright, G., Chan, W. C., Connors, J. M., Campo, E., Fisher, R. I., Gascoyne, R. D., Muller-Hermelink, H. K., Smeland, E. B., Giltnane, J. M., Hurt, E. M., Zhao, H., Averett, L., Yang, L., Wilson, W. H., Jaffe, E. S., Simon, R., Klausner, R. D., Powell, J., Duffey, P. L., Longo, D.L., Greiner, T. C., Weisenburger, D. D., Sanger, W. G., Dave, B. J., Lynch, J. C., Vose, J., Armitage, J. O., Montserrat, E., López-Guillermo, A., Grogan, T. M., Miller, T. P., LeBlanc, M., Ott, G., Kvaloy, S., Delabie, J., Holte, H., Krajci. P., Stokke, T. and Staudt, L. M., The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 2002. 346: 1937-1947.
[14] Savage, K. J., Monti, S., Kutok, J. L., Cattoretti, G., Neuberg, D., De Leval, L., Kurtin, P., Dal Cin, P., Ladd, C., Feuerhake, F., Aguiar, R. C., Li, S., Salles, G., Berger, F., Jing, W., Pinkus, G. S., Habermann, T., Dalla-Favera, R., Harris, N. L., Aster, J.C., Golub, T. R. and Shipp, M. A., The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003. 102: 3871-3879.
[15] Wright, G., Tan, B., Rosenwald, A., Hurt, E. H., Wiestner, A. and Staudt, L. M., A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc. Natl. Acad. Sci. USA 2003. 100: 9991-9996.
[16] Lenz, G., Wright, G. W., Emre, N. C., Kohlhammer, H., Dave, S. S., Davis, R. E., Carty, S., Lam, L. T., Shaffer, A. L., Xiao, W., Powell, J., Rosenwald, A., Ott, G., Muller-Hermelink, H. K., Gascoyne, R. D., Connors, J. M., Campo, E., Jaffe, E. S., Delabie, J., Smeland, E. B., Rimsza, L. M., Fisher, R. I., Weisenburger, D. D., Chan, W. C. and Staudt, L. M., Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc. Natl. Acad. Sci. USA 2008. 105: 13520-13525.
[17] Ross, M. E., Zhou, X., Song, G., Shurtleff, S. A., Girtman, K., Williams, W. K., Liu, H. C., Mahfouz, R., Raimondi, S. C., Lenny, N., Patel, A. and Downing, J. R., Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood 2003. 102: 2951-2959.
[18] Yeoh, E. J., Ross, M. E., Shurtleff, S. A., Williams, W. K., Patel, D., Mahfouz, R., Behm, F. G., Raimondi, S. C., Relling, M. V., Patel, A., Cheng, C., Campana, D., Wilkins, D., Zhou, X., Li, J., Liu, H., Pui, C.H., Evans, W. E., Naeve, C., Wong, L. and Downing, J. R., Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002. 1: 133-143.
[19] Kohlmann, A., Schoch, C., Schnittger, S., Dugas, M., Hiddemann, W., Kern, W. and Haferlach, T., Pediatric acute lymphoblastic leukemia (ALL) gene expression signatures classify an independent cohort of adult ALL patients. Leukemia 2004. 18: 63-71.
[20 ] Kern, W., Kohlmann, A., Schnittger, S., Hiddemann, W., Schoch, C. and Haferlach, T., Gene expression profiling as a diagnostic tool in acute myeloid leukemia. American Journal of Pharmacogenomics: genomics-related research in drug development and clinical practice 2004. 4: 225-237.
[21] Downing, J. R., Wilson, R. K., Zhang, J., Mardis, E. R., Pui, C. H., Ding, L., Ley, T. J. and Evans, W. E., The Pediatric Cancer Genome Project. Nat. Genet. 2012. 44: 619-622.
[22] Morin, R. D., Mungall, K., Pleasance, E., Mungall, A. J., Goya, R., Huff, R. D., Scott, D. W., Ding, J., Roth, A., Chiu, R., Corbett, R. D., Chan, F. C., Mendez-Lago, M., Trinh, D. L., Bolger-Munro, M., Taylor, G., Hadj Khodabakhshi, A., Ben-Neriah, S., Pon, J., Meissner, B., Woolcock, B., Farnoud, N., Rogic, S., Lim, E.L., Johnson, N. A., Shah, S., Jones, S., Steidl, C., Holt, R., Birol, I., Moore, R., Connors, J. M., Gascoyne, R.D. and Marra, M. A., Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood 2013. 122: 1256-1265.

Chapter 5

[1] Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J. and Thun, M. J., Cancer statistics, 2009. CA Cancer J Clin 2009. 59: 225-249.
[2] Hanahan, D. and Weinberg, R. A., Hallmarks of cancer: the next generation. Cell 2011. 144: 646-674.
[3] Boxer, R. B., Jang, J. W., Sintasath, L. and Chodosh, L. A., Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 2004. 6: 577-586.
[4] Chin, L., Tam, A., Pomerantz, J., Wong, M., Holash, J., Bardeesy, N., Shen, Q., O'Hagan, R., Pantginis, J., Zhou, H., Horner, J. W., 2nd, Cordon-Cardo, C., Yancopoulos, G. D. and DePinho, R. A., Essential role for oncogenic Ras in tumour maintenance. Nature 1999. 400: 468-472.
[5] Huettner, C. S., Zhang, P., Van Etten, R. A. and Tenen, D. G., Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 2000. 24: 57-60.
[6] Weinstein, I. B., Cancer. Addiction to oncogenes--the Achilles heal of cancer. Science 2002. 297: 63-64.
[7] Mitelman, F., Johansson, B., and Mertens, F., (Eds.). Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer 2013.
[8] Fialkow, P. J., Jacobson, R. J. and Papayannopoulou, T., Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am J Med 1977. 63: 125-130.
[9] Reya, T., Morrison, S. J., Clarke, M. F. and Weissman, I. L., Stem cells, cancer, and cancer stem cells. Nature 2001. 414: 105-111.
[10] Sanchez-Garcia, I., Vicente-Duenas, C. and Cobaleda C., The theoretical basis of cancer-stem-cell-based therapeutics of cancer: can it be put into practice? Bioessays 2007. 29: 1269-1280.
[11] Hamburger, A. and Salmon, S. E., Primary bioassay of human myeloma stem cells. J Clin Invest 1977. 60: 846-854.
[12] Hamburger, A. W. and Salmon, S. E., Primary bioassay of human tumor stem cells. Science 1977. 197: 461-463.
[13] Bonnet, D. and Dick, J. E., Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997. 7:730-737.
[14] Cobaleda, C. and Sanchez-Garcia, I., B-cell acute lymphoblastic leukaemia: towards understanding its cellular origin. Bioessays 2009. 31: 600-609.
[15] Quintana, E., Shackleton, M., Sabel, M. S., Fullen, D. R., Johnson, T. M. and Morrison, S. J., Efficient tumour formation by single human melanoma cells. Nature 2008. 456: 593-598.
[16] Vicente-Duenas, C., Perez-Caro, M., Abollo-Jimenez, F., Cobaleda, C. and Sanchez-Garcia, I., Stem-cell driven cancer: "hands-off" regulation of cancer development. Cell Cycle 2009. 8: 1314-1318.
[17] Vicente-Dueñas, C., Romero-Camarero, I., Cobaleda, C. and Sánchez-García, I., Function of oncogenes in cancer development: a changing paradigm. EMBO J. 2013. 32:1502-1513.
[18] Perez-Caro, M., Cobaleda, C., Gonzalez-Herrero, I., Vicente-Duenas, C., Bermejo-Rodriguez, C., Sanchez-Beato, M., Orfao, A., Pintado, B., Flores, T., Sanchez-Martin, M., Jimenez, R., Piris. M. A. and Sanchez-Garcia, I., Cancer induction by restriction of oncogene expression to the stem cell compartment. EMBO J. 2009. 28: 8-20.
[19] Barker, N., The canonical Wnt/beta-catenin signalling pathway. Methods Mol Biol 2008. 468: 5-15.
[20] Barker, N., Ridgway, R. A., van Es, J. H., van de Wetering, M., Begthel, H., van den Born, M., Danenberg, E., Clarke, A. R., Sansom, O.J. and Clevers, H., Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009. 457: 608-611.
[21] Zhu, L., Gibson, P., Currle, D.S., Tong, Y., Richardson, R.J., Bayazitov, I. T., Poppleton, H., Zakharenko, S., Ellison, D. W. and Gilbertson, R. J., Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009. 457: 603-607.
[22] Alcantara Llaguno, S., Chen, J., Kwon, C.H., Jackson, E. L., Li, Y., Burns, D. K., Alvarez-Buylla, A. and Parada, L., Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 2009. 15: 45-56.
[23] Dirks, P. B., Cancer's source in the peripheral nervous system. Nat Med 2008. 14: 373-375.
[24] Joseph, N. M., Mosher, J. T., Buchstaller, J., Snider, P., McKeever, P. E., Lim, M, Conway S. J, Parada L. F, Zhu Y, Morrison S. J., The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell 2008. 13: 129-140.
[25] Zheng, H., Ying, H., Yan, H., Kimmelman, A. C., Hiller, D.J., Chen, A. J., Perry, S. R., Tonon, G., Chu, G. C., Ding, Z., Stommel, J. M., Dunn, K. L., Wiedemeyer, R., You, M. J., Brennan, C., Wang, Y. A., Ligon, K. L., Wong, W. H., Chin, L. and dePinho, R. A., Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harb Symp Quant Biol 2008. 73: 427-437.
[26] Huntly, B. J., Shigematsu, H., Deguchi, K., Lee, B.H., Mizuno, S., Duclos, N., Rowan, R., Amaral, S., Curley, D., Williams, I. R., Akashi, K. and Gilliland, D. G., MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 2004. 6: 587-596.
[27] Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W.C., Gilliland, D.G., Golub, T.R. and Armstrong, S. A., Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006. 442: 818-822.
[28] Somervaille, T. C. and Cleary, M. L., Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia. Cancer Cell 2006. 10: 257-226.
[29] Cozzio, A., Passegue, E., Ayton, P. M., Karsunky, H., Cleary, M. L. and Weissman, I. L., Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 2003. 17: 3029-3035.
[30] So, C. W., Karsunky, H., Passegue, E., Cozzio, A., Weissman, I. L. and Cleary, M. L., MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 2003. 3: 161-171.
[31] Guibal, F. C., Alberich-Jorda, M., Hirai, H., Ebralidze, A., Levantini, E., Di Ruscio, A., Zhang, P., Santana-Lemos, B. A., Neuberg, D., Wagers, A.J., Rego, E. M. and Tenen, D. G., Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood 2009. 114: 5415-5425.
[32] Wojiski, S., Guibal, F. C., Kindler, T., Lee, B. H., Jesneck, J. L., Fabian, A., Tenen, D. G. and Gilliland, D. G., PML-RARalpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors. Leukemia 2009. 23: 1462-1471.
[33] Wong, D. J., Liu, H., Ridky, T. W., Cassarino, D., Segal, E. and Chang, H. Y., Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2208. 2: 333-344.
[34] Chen, L., Shen, R., Ye, Y., Pu, X. A., Liu, X., Duan, W., Wen, J., Zimmerer, J., Wang, Y., Liu, Y., Lasky, L.C., Heerema, N.A., Perrotti, D., Ozato, K., Kuramochi-Miyagawa, S., Nakano, T., Yates, A.J., Carson, W.E., 3rd, Lin, H., Barsky, S.H. and Gao, J. X., Precancerous stem cells have the potential for both benign and malignant differentiation. PLoS One 2007. 2: e293.
[35] Schwitalla, S., Fingerle, A. A., Cammareri, P., Nebelsiek, T., Goktuna, S.I., Ziegler, P. K., Canli, O., Heijmans, J., Huels, D. J., Moreaux, G., Rupec, R.A., Gerhard, M., Schmid, R., Barker, N., Clevers, H., Lang, R., Neumann, J., Kirchner, T., Taketo, M.M., van den Brink, G. R., Sansom, O. J., Arkan, M. C. and Greten, F. R., Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties. Cell 2013. 152: 25-38.
[36] Bazzoli, E., Pulvirenti, T., Oberstadt, M. C., Perna, F., Wee, B., Schultz, N., Huse, J. T., Fomchenko, E. I., Voza, F., Tabar, V., Brennan, C. W., DeAngelis, L. M., Nimer, S. D., Holland, E. C. and Squatrito, M., MEF promotes stemness in the pathogenesis of gliomas. Cell Stem Cell 2012. 11: 836-844.
[37] Friedmann-Morvinski, D., Bushong, E. A., Ke, E., Soda, Y., Marumoto, T., Singer, O., Ellisman, M. H. and Verma, I. M., Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 2012. 338: 1080-1084.
[38] Hatley, M. E., Tang, W., Garcia, M. R., Finkelstein, D., Millay, D. P., Liu, N., Graff, J., Galindo, R. L. and Olson, E. N., A mouse model of rhabdomyosarcoma originating from the adipocyte lineage. Cancer Cell 2012. 22: 536-546.
[39] Youssef, K. K., Lapouge, G., Bouvree, K., Rorive, S., Brohee, S., Appelstein, O., Larsimont, J. C., Sukumaran, V., Van de Sande, B., Pucci, D., Dekoninck, S., Berthe, J. V., Aerts, S., Salmon, I., del Marmol, V. and Blanpain, C., Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation. Nat Cell Biol 2012. 14: 1282-1294.
[40] Scaffidi, P. and Misteli, T., In vitro generation of human cells with cancer stem cell properties. Nat Cell Biol 2011. 13: 1051-1061.
[41] Hong, D., Gupta, R., Ancliff, P., Atzberger, A., Brown, J., Soneji, S., Green, J., Colman, S., Piacibello, W., Buckle, V., Tsuzuki, S., Greaves, M. and Enver, T., Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science 2008. 319: 336-339.
[42] Miyamoto, T., Weissman, I. L. and Akashi, K., AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci U S A 2000. 97: 7521-7526.
[43] Cobaleda, C., Jochum, W. and Busslinger M., Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 2007. 449: 473-477.
[44] Mathas, S., Janz, M., Hummel, F., Hummel, M., Wollert-Wulf, B., Lusatis, S., Anagnostopoulos, I., Lietz, A., Sigvardsson, M., Jundt, F., Johrens, K., Bommert, K., Stein, H. and Dorken, B., Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma. Nat Immunol 2006. 7: 207-215.
[45] le Viseur, C., Hotfilder, M., Bomken, S., Wilson, K., Rottgers, S., Schrauder, A., Rosemann, A., Irving, J., Stam, R.W., Shultz, L. D., Harbott, J., Jurgens, H., Schrappe, M., Pieters, R. and Vormoor, J., In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties. Cancer Cell 2008. 14: 47-58.
[46] Mullighan, C. G., Phillips, L. A., Su, X., Ma, J., Miller, C.B., Shurtleff, S. A. and Downing, J. R., Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 2008. 322: 1377-1380.
[47] Greaves, M., Cancer stem cells: back to Darwin? Semin Cancer Biol 2010. 20: 65-70.
[48] Brown, G. and Sanchez-Garcia, I., Is lineage decision-making restricted during tumoral reprograming of haematopoietic stem cells? Oncotarget 2015. 6: 43326-43341.
[49] Sánchez-García, I., Getting to the stem of cancer. Semin Cancer Biol. 2010. 20: 63-64.
[50] Sánchez-García, I., How tumour cell identity is established? Semin Cancer Biol. 2015. 32: 1-2.
[51] Vicente-Dueñas, C., Hauer, J., Ruiz-Roca, L., Ingenhag, D., Rodríguez-Meira, A., Auer, F., Borkhardt, A. and Sánchez-García, I., Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy. Semin Cancer Biol. 2015. 32: 3-9.

Chapter 6

[1] Hanna, J., Carey, B.W. and Jaenisch, R., Reprogramming of Somatic Cell Identity. Cold Spring Harb. Symp. Quant. Biol. 2008. 73: 147-155.
[2] Krizhanovsky, V. and Lowe, S. W. Stem cells: The promises and perils of p53. Nature 2009. 460: 1085-1086.
[3] Perez-Caro, M., Cobaleda, C., Gonzalez-Herrero, I., Vicente-Duenas, C., Bermejo-Rodriguez, C., Sanchez-Beato, M., Orfao, A., Pintado, B., Flores, T., Sanchez-Martin, M., Jimenez, R., Piris, M. A. and Sanchez-Garcia, I., Cancer induction by restriction of oncogene expression to the stem cell compartment. EMBO J. 2009. 28: 8-20.
[4] Romero-Camarero, I., Jiang, X., Natkunam, Y., Lu, X., Vicente-Duenas, C., Gonzalez-Herrero, I., Flores, T., Luis Garcia, J., McNamara, G., Kunder, C., Zhao, S., Segura, V., Fontan, L., Martinez-Climent, J. A., Javier Garcia-Criado, F., Theis, J. D., Dogan, A., Campos-Sanchez, E., Green, M. R., Alizadeh, A. A., Cobaleda, C., Sanchez-Garcia, I. and Lossos, I. S., Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. Nat. Commun. 2013. 4: 1338.
[5] Vicente-Duenas, C., Fontan, L., Gonzalez-Herrero, I., Romero-Camarero, I., Segura, V., Aznar, M. A., Alonso-Escudero, E., Campos-Sanchez, E., Ruiz-Roca, L., Barajas-Diego, M., Sagardoy, A., Martinez-Ferrandis, J. I., Abollo-Jimenez, F., Bertolo, C., Penuelas, I., Garcia-Criado, F. J., Garcia-Cenador, M. B., Tousseyn, T., Agirre, X., Prosper, F., Garcia-Bragado, F., McPhail, E. D., Lossos, I. S., Du, M. Q., Flores, T., Hernandez-Rivas, J. M., Gonzalez, M., Salar, A., Bellosillo, B., Conde, E., Siebert, R., Sagaert, X., Cobaleda, C., Sanchez-Garcia, I. and Martinez-Climent, J. A., Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice. Proc. Natl. Acad. Sci. USA 2012. 109: 10534-10539.
[6] Vicente-Duenas, C., Romero-Camarero, I., Gonzalez-Herrero, I., Alonso-Escudero, E., Abollo-Jimenez, F., Jiang, X., Gutierrez, N. C., Orfao, A., Marin, N., Villar, L. M., Criado, M. C., Pintado, B., Flores, T., Alonso-Lopez, D., De Las Rivas, J., Jimenez, R., Criado, F. J., Cenador, M. B., Lossos, I. S., Cobaleda, C. and Sanchez-Garcia, I., A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors. Embo J. 2012. 31: 3704-3717.
[7] Riggi, N., Suva, M. L., De Vito, C., Provero, P., Stehle, J. C., Baumer, K., Cironi, L., Janiszewska, M., Petricevic, T., Suva, D., Tercier, S., Joseph, J. M., Guillou, L. and Stamenkovic, I., EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010. 24: 916-932.
[8] Garcia, C. B., Shaffer, C. M., Alfaro, M. P., Smith, A. L., Sun, J., Zhao, Z., Young, P. P., VanSaun, M. N. and Eid, J. E., Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2. Oncogene 2012. 31: 2323-2334.
[9] Kikushige, Y., Ishikawa, F., Miyamoto, T., Shima, T., Urata, S., Yoshimoto, G., Mori, Y., Iino, T., Yamauchi, T., Eto, T., Niiro, H., Iwasaki, H., Takenaka, K. and Akashi, K., Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell 2011. 20: 246-259.
[10] Corbin, A. S., Agarwal, A., Loriaux, M., Cortes, J., Deininger, M. W. and Druker, B. J., Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J. Clin. Invest. 2011. 121: 396-409.
[11] Chomel, J. C., Bonnet, M. L., Sorel, N., Bertrand, A., Meunier, M. C., Fichelson, S., Melkus, M., Bennaceur-Griscelli, A., Guilhot, F. and Turhan, A. G., Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease. Blood 2011. 118: 3657-3660.
[12] Chu, S., McDonald, T., Lin, A., Chakraborty, S., Huang, Q., Snyder, D. S. and Bhatia, R. Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment. Blood 2011. 118: 5565-5572.
[13] Hamilton, A., Helgason, G. V., Schemionek, M., Zhang, B., Myssina, S., Allan, E. K., Nicolini, F. E., Muller-Tidow, C., Bhatia, R., Brunton, V. G., Koschmieder, S. and Holyoake, T. L., Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood 2012. 119: 1501-1510.
[14] Kumari, A., Brendel, C., Hochhaus, A., Neubauer, A. and Burchert, A., Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib. Blood 2012. 119: 530-539.
[15] Barnes, D. J. and Melo, J.V., Primitive, quiescent and difficult to kill: the role of non-proliferating stem cells in chronic myeloid leukemia. Cell Cycle 2006. 5: 2862-2866.
[16] Graham, S. M., Jorgensen, H. G., Allan, E., Pearson, C., Alcorn, M. J., Richmond, L. and Holyoake, T. L., Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002. 99: 319-325.
[17] Sanchez-Garcia, I., The crossroads of oncogenesis and metastasis. N. Engl. J. Med. 2009. 360: 297-299.
[18] Alizadeh, A. A. and Majeti, R., Surprise! HSC are aberrant in chronic lymphocytic leukemia. Cancer Cell 2011. 20: 135-136.
[19] Ben-David, U., Mayshar, Y. and Benvenisty, N., Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells. Cell Stem Cell 2011. 9: 97-102.
[20] Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., Perna, F., Pandey, S., Madzo, J., Song, C., Dai, Q., He, C., Ibrahim, S., Beran, M., Zavadil, J., Nimer, S, D., Melnick, A., Godley, L. A., Aifantis, I. and Levine, R. L., Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 2011. 20: 11-24.
[21] Banito, A., Rashid, S. T., Acosta, J. C., Li, S., Pereira, C. F., Geti, I., Pinho, S., Silva, J. C., Azuara, V., Walsh, M., Vallier, L. and Gil, J., Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev. 2009. 23: 2134-2139.
[22] Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K. and Yamanaka, S., Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 2009. 460: 1132-1135.
[23] Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Canamero, M., Blasco, M. A. and Serrano, M., The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 2009. 460: 1136-1139.
[24] Marion, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M. and Blasco, M. A., A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 2009. 460: 1149-1153.
[25] Utikal, J., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G. and Hochedlinger, K., Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 2009. 460: 1145-1148.
[26] Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang. W., Zhang, Q., Xiang, C., Hou, P., Song, Z., Liu, Y., Yong, J., Zhang, P., Cai, J., Liu, M., Li, H., Li, Y., Qu, X., Cui, K., Zhang, W., Xiang, T., Wu, Y., Liu, C., Yu, C., Yuan, K., Lou, J., Ding, M. and Deng, H., Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 2008. 3: 475-479.
[27] Velasco-Hernandez, T., Vicente-Duenas, C., Sanchez-Garcia, I. and Martin-Zanca, D., p53 restoration kills primitive leukemia cells in vivo and increases survival of leukemic mice. Cell Cycle 2013. 12: 122-132.
[28] Vicente-Duenas, C., Gonzalez-Herrero, I., Cenador, M. B., Criado, F. J. and Sanchez-Garcia, I., Loss of p53 exacerbates multiple myeloma phenotype by facilitating the reprogramming of hematopoietic stem/progenitor cells to malignant plasma cells by MafB. Cell Cycle 2012. 11: 3896-3900.
[29] Feinberg, A. P., Ohlsson, R. and Henikoff, S., The epigenetic progenitor origin of human cancer. Nat. Rev. Genet. 2006. 7: 21-33.
[30] Iacobuzio-Donahue, C. A., Epigenetic changes in cancer. Ann. Rev. Pathol. 2009. 4: 229-249.
[31] Shearstone, J. R., Pop, R., Bock, C., Boyle, P., Meissner, A. and Socolovsky, M., Global DNA demethylation during mouse erythropoiesis in vivo. Science 2011. 334: 799-802.
[32] Hochedlinger, K., Blelloch, R., Brennan, C., Yamada, Y., Kim, M., Chin, L., and Jaenisch, R., Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev 2004. 18: 1875-1885.
[33] Blelloch, R.H., Hochedlinger, K., Yamada, Y., Brennan, C., Kim, M., Mintz, B., Chin, L. and Jaenisch, R., Nuclear cloning of embryonal carcinoma cells. Proc. Natl. Acad. Sci. USA 101: 13985-13990.
[34] Li, L., Connelly, M.C., Wetmore, C., Curran, T. and Morgan, J. I., Mouse embryos cloned from brain tumors. Cancer Res. 2003. 63, 2733-2736.
[35] Stricker, S. H., Feber, A., Engström, P. G., Carén, H., Kurian, K. M., Takashima, Y., Watts, C., Way, M., Dirks, P., Bertone, P., Smith, A., Beck, S. and Pollard S. M., Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner. Genes Dev. 2013. 27: 654-669.
[36] Etzioni, R., Urban, N., Ramsey, S., McIntosh, M., Schwartz, S., Reid, B., Radich, J., Anderson, G. and Hartwell, L., The case for early detection. Nat. Rev. Cancer 2003. 3: 243-252.
[37] Jemal, A., Siegel, R., Ward, E., Hao, Y., and Xu, J., Thun M. J., Cancer Statistics, 2009. CA. Cancer. J. Clin. 2009. 59: 225-249.
[38] Walker, C. L. and Ho, S. M., Developmental reprogramming of cancer susceptibility. Nat. Rev. Cancer. 2012. 12: 479-486.

Chapter 7

[1] Etzioni, R., Urban, N., Ramsey, S., McIntosh, M., Schwartz, S., Reid, B., Radich, J., Anderson, G. and Hartwell, L., The case for early detection. Nat. Rev. Cancer 2003. 3:243-252.
[2] Cobaleda, C. and Sanchez-Garcia, I., B-cell acute lymphoblastic leukaemia: towards understanding its cellular origin. Bioessays 2009. 31: 600-609.
[3] Dalerba, P., Cho, R. W. and Clarke, M. F., Cancer stem cells: models and concepts. Ann. Rev. Med. 2007. 58:267-84.
[4] Reya, T., Morrison, S.J., Clarke, M. F. and Weissman, I. L., Stem cells, cancer, and cancer stem cells. Nature 2001. 414: 105-111.
[5] Perez-Caro, M. and Sanchez-Garcia, I., Killing time for cancer stem cells (CSC): discovery and development of selective CSC inhibitors. Curr. Med. Chem. 2006. 13: 1719-1725.
[6] Chabner, B. A. and Roberts, T. G. Jr., Timeline: Chemotherapy and the war on cancer. Nat. Rev. Cancer 2005. 5:65-72.
[7] Bonnet, D. and Dick, J. E., Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 1997. 3:730-737.
[8] Hope, K. J., Jin, L. and Dick, J. E., Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat. Immunol. 2004. 5: 738-743.
[9] Miyamoto, T., Weissman, I. L and Akashi, K., AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc. Natl. Acad. Sci. USA 2000. 97: 7521-7526.
[10] Cobaleda, C., Gutierrez-Cianca, N., Perez-Losada, J., Flores, T., Garcia-Sanz, R., González, M. and Sánchez-García, I., A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Blood 2000. 95: 1007-1013.
[11] Cox, C. V., Evely, R. S., Oakhill, A., Pamphilon, D. H., Goulden, N. J. and Blair A., Characterization of acute lymphoblastic leukemia progenitor cells. Blood 2004. 104: 2919-2925.
[12] Cox, C. V., Martin, H. M., Kearns, P. R., Virgo, P., Evely, R. S. and Blair A., Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood 2007. 109: 674-682.
[13] Ren, R., Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat. Rev. Cancer 2005. 5: 172-183.
[14] Melo, J. V. and Barnes, D. J., Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat. Rev. Cancer 2007. 7: 441-453.
[15] Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. and Clarke, M. F., Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003. 100: 3983-3988.
[16] Dick, J. E., Breast cancer stem cells revealed. Proc. Natl. Acad. Sci. USA 2003. 100: 3547-3549.
[17] Dalerba, P., Dylla, S. J., Park, I. K., Liu, R., Wang, X., Cho, R. W., Hoey, T., Gurney, A., Huang, E. H., Simeone, D.M., Shelton, A. A., Parmiani, G., Castelli, C. and Clarke, M. F., Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl. Acad. Sci. USA 2007. 104: 10158-10163.
[18] O'Brien, C.A., Pollett, A., Gallinger, S. and Dick, J. E., A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007. 445: 106-110.
[19] Ricci-Vitiani, L., Lombardi, D. G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C. and De Maria, R., Identification and expansion of human colon-cancer-initiating cells. Nature 2007. 445: 111-115.
[20] Bao, S., Wu, Q., McLendon, R. E., Hao, Y., Shi, Q., Hjelmeland, A. B., Dewhirst, M. W., Bigner, D. D. and Rich, J.N., Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006. 444: 756-760.
[21] Bao, S., Wu, Q., Sathornsumetee, S., Hao, Y., Li, Z., Hjelmeland, A. B., Shi, Q., McLendon, R. E., Bigner, D. D. and Rich, J. N., Stem Cell-like Glioma Cells Promote Tumor Angiogenesis through Vascular Endothelial Growth Factor. Cancer Res. 2006. 66: 7843-7848.
[22] Singh, S. K., Hawkins, C., Clarke, I. D., Squire, J. A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D. and Dirks, P.B., Identification of human brain tumour initiating cells. Nature 2004. 432: 396-401.
[23] Piccirillo, S. G., Reynolds, B. A., Zanetti, N., Lamorte, G., Binda, E., Broggi, G., Brem, H., Olivi, A., Dimeco, F. and Vescovi, A. L., Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 2006. 444: 761-765.
[24] Li, C., Heidt, D. G., Dalerba, P., Burant, C. F., Zhang, L., Adsay, V., Wicha, M., Clarke, M.F. and Simeone, D.M., Identification of pancreatic cancer stem cells. Cancer Res. 2007. 67: 1030-1037.
[25] Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P., Weissman, I. L., Clarke, M. F. and Ailles, L. E., Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc. Natl. Acad. Sci. USA 2007. 104: 973-978.
[26] Kim, C. F., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., Crowley, D., Bronson, R. T. and Jacks, T., Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005. 121: 823-835.
[27] Collins, A. T., Berry, P. A., Hyde, C., Stower, M. J. and Maitland, N. J., Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005. 65: 10946-10951.
[28] Brown, G. and Sanchez-Garcia, I., Is lineage decision-making restricted during tumoral reprograming of haematopoietic stem cells? Oncotarget 2015. 6:43326-43341.
[29] Vicente-Dueñas, C., Hauer, J., Ruiz-Roca, L., Ingenhag, D., Rodríguez-Meira, A., Auer, F., Borkhardt, A. and Sánchez-García, I., Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy. Semin. Cancer Biol. 2015. 32: 3-9.
[30] Sanchez-Garcia, I., How tumour cell identity is established? Semin. Cancer Biol. 2015. 32

: 1-2.
[31] Dean, M., Fojo, T. and Bates, S., Tumour stem cells and drug resistance. Nat. Rev. Cancer 2005. 5: 275-284.
[32] Cohnheim, J., Ueber entzundung und eiterung. Path. Anat. Physiol. Klin. Med. 1867. 40: 1-79.
[33] Virchow, R., Editorial. Virchows Arch. Pathol. Anat. Physiol. Med. 1885.
[34] Vicente-Duenas, C., Romero-Camarero, I., Cobaleda, C. and Sanchez-Garcia, I., Function of oncogenes in cancer development: a changing paradigm. EMBO J. 2013. 32: 1502-1513.
[35] Pérez-Caro, M., Cobaleda, C., González-Herrero, I., Vicente-Dueñas, C., Bermejo-Rodríguez, C., Sánchez-Beato, M., Orfao, A., Pintado, B., Flores, T., Sánchez-Martín, M., Jiménez, R., Piris, M, A. and Sánchez-García, I., Cancer induction by restriction of oncogene expression to the stem cell compartment. EMBO J. 2009. 28: 8-20.
[36] Vicente-Duenas, C., Perez-Caro, M., Abollo-Jimenez, F., Cobaleda, C. and Sanchez-Garcia, I., Stem-cell driven cancer: "hands-off" regulation of cancer development. Cell Cycle. 2009. 8: 1314-1318.


[37] Vicente-Duenas, C., Gonzalez-Herrero, I., Cenador, M. B., Criado, F. J. and Sanchez-Garcia, I., Loss of p53 exacerbates multiple myeloma phenotype by facilitating the reprogramming of hematopoietic stem/progenitor cells to malignant plasma cells by MafB. Cell Cycle. 2012. 11: 3896-3900.
[38] Vicente-Dueñas, C., Romero-Camarero, I., González-Herrero, I., Alonso-Escudero, E., Abollo-Jiménez, F., Jiang, X., Gutierrez, N. C., Orfao, A., Marín, N., Villar, L. M., Criado, M. C., Pintado, B., Flores, T., Alonso-López, D., De Las Rivas, J., Jiménez, R., Criado, F.J., Cenador, M.B., Lossos, I.S., Cobaleda, C. and Sánchez-García, I., A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors. EMBO J. 2012. 31: 3704-3717.
[39] Vicente-Dueñas, C., Fontán, L., Gonzalez-Herrero, I., Romero-Camarero, I., Segura, V., Aznar, M. A., Alonso-Escudero, E., Campos-Sanchez, E., Ruiz-Roca, L., Barajas-Diego, M., Sagardoy, A., Martinez-Ferrandis, J. I., Abollo-Jimenez, F., Bertolo, C., Peñuelas, I., Garcia-Criado, F.J., García-Cenador, M.B., Tousseyn, T., Agirre, X., Prosper, F., Garcia-Bragado, F., McPhail, E.D., Lossos, I.S., Du, M.Q., Flores, T., Hernandez-Rivas, J. M., Gonzalez, M., Salar, A., Bellosillo, B., Conde, E., Siebert, R., Sagaert, X., Cobaleda, C., Sanchez-Garcia, I. and Martinez-Climent, J. A., Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice. Proc. Natl. Acad. Sci. USA. 2012. 109: 10534-10539.
[40] Velasco-Hernandez, T., Vicente-Duenas, C., Sanchez-Garcia, I. and Martin-Zanca, D., p53 restoration kills primitive leukemia cells in vivo and increases survival of leukemic mice. Cell Cycle. 2012. 12: 122-132.
[41] Romero-Camarero, I., Jiang, X., Natkunam, Y., Lu, X., Vicente-Dueñas, C., Gonzalez-Herrero, I., Flores, T., Garcia, J. L., McNamara, G., Kunder, C., Zhao, S., Segura, V., Fontan, L., Martínez-Climent, J. A., García-Criado, F. J., Theis, J. D., Dogan, A., Campos-Sánchez, E., Green, M. R., Alizadeh, A. A., Cobaleda, C., Sánchez-García, I. and Lossos, I. S., Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. Nat. Commun. 2013. 4: 1338.
[42] Green, M. R., Vicente-Dueñas, C., Romero-Camarero, I., Long Liu, C., Dai, B., González-Herrero, I., García-Ramírez, I., Alonso-Escudero, E., Iqbal, J., Chan, W. C., Campos-Sanchez, E., Orfao, A., Pintado, B., Flores, T., Blanco, O., Jiménez, R., Martínez-Climent, J. A., Criado, F. J., Cenador, M.B., Zhao, S., Natkunam, Y., Lossos, I. S., Majeti, R., Melnick, A., Cobaleda, C., Alizadeh, A. A. and Sánchez-García, I., Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma. Nat. Commun. 2014. 5: 3904.
[43] Prost, S., Relouzat, F., Spentchian, M., Ouzegdouh, Y., Saliba, J., Massonnet, G., Beressi, J. P., Verhoeyen, E., Raggueneau, V., Maneglier, B., Castaigne, S., Chomienne, C., Chrétien, S., Rousselot, P. and Leboulch, P., Erosion of the chronic myeloid leukaemia stem cell pool by PPARg agonists. Nature 2015. 525:380-383.
[44] Hauer, J., Martín-Lorenzo, A. and Sánchez-García, I., Infection causes childhood leukemia. Aging (Albany NY) 2015. 7(9):607-608.
[45] Martin-Lorenzo, A., Hauer, J., Vicente-Duenas, C., Auer, F., Gonzalez-Herrero, I., Garcia-Ramirez, I., Ginzel, S., Thiele, R., Constantinescu, S. N., Bartenhagen, C., Dugas, M., Gombert, M., Schafer, D., Blanco, O., Mayado, A., Orfao, A., Alonso-López, D., Rivas, J. de L., Cobaleda, C., García-Cenador, M. B., García-Criado, F. J., Sánchez-García, I. and Borkhardt, A., Infection Exposure Is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility. Cancer Discov. 2015. 5:1328-1343.
[46] Waddington, C. H., The Strategy of Genes; a Discussion of Some Aspects of Theoretical Biology 1957. London: Allen & Unwin.
[47] Yoo, C. B. and Jones, P. A., Epigenetic therapy of cancer: past, present and future. Nat. Rev. Drug. Discov. 2006. 5: 37-50.
[48] Greenblatt, S. M and Nimer, S. D., Chromatin modifiers and the promise of epigenetic therapy in acute leukemia. Leukemia 2014. 28: 1396-1406.
[49] Saito, Y., Liang, G., Egger, G., Friedman, J. M., Chuang, J, C., Coetzee, G. A. and Jones, P. A., Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 2006. 9: 435-43.
[50] Asangani, I. A., Ateeq, B., Cao, Q., Dodson, L., Pandhi, M., Kunju, L. P., Mehra, R., Lonigro, R. J., Siddiqui, J., Palanisamy, N., Wu, Y. M., Cao, X., Kim, J. H., Zhao, M., Qin, Z. S., Iyer, M. K., Maher, C. A., Kumar-Sinha, C., Varambally, S. and Chinnaiyan, A. M., Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer. Mol. Cell 2013. 49: 80-93.
[51] Sánchez

-García, I., Getting to the stem of cancer. Semin. Cancer Biol. 2010. 20: 63-64.


We believe that our book will be of great interest to A) teaching activities at undergraduate and postgraduate levels at universities (Schools of Medicine, Biological Science, etc) and to B) a number of junior (postdoctoral) and senior researchers including (i) medical doctors, due to the importance of an understanding of normal stem cells and Cancer Stem Cells to both the preclinical and clinical fields; (ii) stem cell researchers because of their intrinsic interest in the principles that govern the behaviour of normal stem cells and CSCs and their importance to biology, (iii) cancer biologists due to the implications of the results discussed in the book to the development of an understanding of the underlying problem in cancer development and (iv) Pharma companies due to the implications of the new ideas to drug discovery.

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