Fetal Hemoglobin: The Panacea for Major β-Hemoglobinopathies

Nishant Chakravorty (Editor)
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India

Series: Recent Advances in Hematology Research
BISAC: MED038000

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Special issue: Resilience in breaking the cycle of children’s environmental health disparities
Edited by I Leslie Rubin, Robert J Geller, Abby Mutic, Benjamin A Gitterman, Nathan Mutic, Wayne Garfinkel, Claire D Coles, Kurt Martinuzzi, and Joav Merrick

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Intricate processes involved in perpetuating the multitude of physiological phenomena in the human body often encounter aberrations and omissions in the genetic code of life. While such errors often lead to lethal diseases, at other times they provide distinctive survival advantages and thus unscramble cues to unconventional therapeutic strategies for life-threatening conditions. Hereditary Persistence of Fetal Hemoglobin (HPFH) is one such condition wherein the typically inactivated fetal form of hemoglobin (HbF) remains overexpressed even in adult stages of the bearer’s life. Strikingly, this condition is known to ameliorate pathological manifestations in patients with aberrant adult hemoglobin synthesis (e.g. β-hemoglobinopathies like β-thalassemia, sickle cell disease etc.). Early researchers in the field expected such patients to suffer from clinical challenges owing to HbF’s high affinity to oxygen and consequent difficulty in its release to cells and tissues. Surprisingly, these patients are known to lead a physiologically normal life. Modern-day hematologists and clinical researchers have looked-up to the concept of “HbF reactivation” as a potential curative strategy for patients suffering from β-hemoglobinopathies like β-thalassemia and sickle cell disease. As a result, several drugs like hydroxyurea, 5-azacytidine, cytosine arabinoside, natural products etc. have been tried in clinics to elevate HbF levels in such patients with limited success and poor understanding on the mechanisms of their action. Associated side-effects and complications of using cytotoxic agents like these restrict their use in most instances. Fortunately, with the advent of newer molecular tools and techniques, researchers are focusing their attention to reengineer the molecular machinery and thus reactivate the gamma-globin gene. This book brings together a selection of chapters dedicated to fetal hemoglobin – its physiological role, regulation, methodologies to manipulate and future strategies. Researchers and scientists interested in the topic will have a comprehensive understanding of the current concepts on fetal hemoglobin modulation and therefore will serve as a launching pad for their research ideas.
(Imprint: Nova Medicine and Health)

Dedication

Preface

Acknowledgements

Chapter 1. Hemoglobin: A Biochemical and Molecular Overview
(Motiur Rahaman, Sankha Subhra Das, Suman Kumar Ray, Ronak Reshamwala and Nishant Chakravorty, School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India, and others)

Chapter 2. Prenatal and Postnatal Hemoglobins: Formation and Gaseous Exchange
(Megha Shah, Ronak Reshamwala, Indra Neil Choudhury and Motiur Rahaman, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia, and others)

Chapter 3. An Introduction to Fetal Hemoglobin and Its Characteristics
(Suman Kumar Ray, Shalini Sanyal, Rashmi Sinha and Nishant Chakravorty, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India, and others)

Chapter 4. Regulation of the Gamma Globin Gene: Current Concepts and Perspectives
(Anindita Basak and Suman Kumar Ray, Boston Children’s Hospital, Harvard Medical School, Boston, MA, US, and others)

Chapter 5. Role of Cell Signaling Pathways in Fetal Hemoglobin Regulation in Beta-Hemoglobinopathies
(Sankha Subhra Das and Nishant Chakravorty, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal, India)

Chapter 6. Molecular Tools for Editing Globin Genes
(Kshitiz Singh, Center for Fetal Research, Children’s Hospital of Philadelphia, Philadelphia, PA, US)

Chapter 7. Genetic Modifiers of Fetal Hemoglobin and Their Role in Alleviating the Clinical Severity of Hemoglobinopathies
(Anita Nadkarni and Priya Hariharan, Department of Hematogenetics, National Institute of Immunohematology, Mumbai, Maharashtra, India)

Chapter 8. Therapeutic Induction of Fetal Hemoglobin Expression: Methods in Practice and Newer Modalities
(Rudra Ray and Maitreyee Bhattacharyya, Institute of Haematology and Transfusion Medicine, Medical College Kolkata, Kolkata, West Bengal, India)

Chapter 9. Genetic Modifiers of β-Thalassemia and Their Therapeutic Implications
(J. W. Nirmani Yasara and Sachith Mettananda, Department of Paediatrics, University of Kelaniya, Ragama, Sri Lanka)

Chapter 10. Clinical Management of β-thalassemia
(Sachith Mettananda and, Hashan Pathiraja, Department of Paediatrics, University of Kelaniya, Ragama, Sri Lanka)

Chapter 11. Current Practices in the Management of Beta-Hemoglobinopathies
(Manisha Jain, Ankit Jitani and Tuphan Kanti Dolai, Department of Haematology, Nil Ratan Sircar Medical College and Hospital, Kolkata, India)

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