ACUTE LEUKEMIA – THE SCIENTIST'S PERSPECTIVE AND CHALLENGE Edited by Mariastefania Antica Acute Leukemia – The Scientist's Perspective and Challenge Edited by Mariastefania Antica Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Petra Nenadic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team Image Copyright Eraxion, 2011. DepositPhotos First published December, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Acute Leukemia – The Scientist's Perspective and Challenge, Edited by Mariastefania Antica p. cm. ISBN 978-953-307-553-2 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Introduction 1 Chapter 1 Classification of Acute Leukemia 3 Gamal Abdul-Hamid Chapter 2 Diagnosis of Acute Leukemia in Under-Resourced Laboratories 19 Abbas H. Abdulsalam Part 2 Molecular Mechanisms and Markers 41 Chapter 3 The PI3K/PKB Signaling Module in Normal and Malignant Hematopoiesis 43 Roel Polak and Miranda Buitenhuis Chapter 4 Lymphocyte Commitment and Ikaros Transcription Factors 69 Mariastefania Antica Chapter 5 Epigenetics and Targeted Therapy in Acute Leukemia 75 Xudong Ma, Shaohong Jiang, Yiqun Huang, Yong Zou, Ruiji Zheng and Liyun Xiao Chapter 6 Molecular Markers for Risk Stratification in Adult Acute Myeloid Leukemia with Normal Cytogenetics 95 Ota Fuchs Chapter 7 Trafficking of Acute Leukemia Cells – Chemokine Receptor Pathways that Modulate Leukemia Cell Dissemination 137 Seiji Fukuda, Chie Onishi and Louis M. Pelus VI Contents Chapter 8 Biochemistry of the Mixed Lineage Leukemia 1 (MLL1) Protein and Targeted Therapies for Associated Leukemia 157 Venkatasubramanian Dharmarajan and Michael S. Cosgrove Part 3 Pediatric Acute Leukemia 205 Chapter 9 Diagnostics of Molecular Markers in Childhood Acute Leukaemia Using Biochips 207 Tatyana Nasedkina, Yuliya Yatsenko, Olga Gra, Natalia Guseva, Elena Samochatova and Alexander Zasedatelev Chapter 10 Pediatric Acute Myeloid Leukemia 235 C. Michel Zwaan and Marry M. van den Heuvel-Eibrink Chapter 11 Pediatric Natural Killer Cell Malignancy 277 Yoshiko Hashii Chapter 12 Leukemogenesis in Down Syndrome 295 Lílian Barros Queiroz, Íris Ferrari, Cezar Martins de Sá, Juliana Forte Mazzeu, Isis Quezado Magalhães and Beatriz Dolabela de Lima Part 4 Treatment and Future Prospects 313 Chapter 13 Cord Blood Transplantation in Adults with Acute Leukemia 315 Takaaki Konuma and Satoshi Takahashi Chapter 14 Acute Lymphoblastic Leukemia in Adolescents and Young Adults 339 Josep-Maria Ribera Chapter 15 Evidence-Based Guided Interventions in Acute Leukemia 349 Ron Ram, Liat Vidal, Ronit Gurion, Pia Raanani and Ofer Shpilberg Chapter 16 Hematologic Malignancies in Pregnancy 371 C. Vandenbriele, A. Vassou, G. Pentheroudakis, K. Van Calsteren and F. Amant Chapter 17 Chemotherapy Toxicity in Patients with Acute Leukemia 391 Jose Manuel Vagace and Guillermo Gervasini Chapter 18 Vitamin D and Acute Myeloid Leukemia 415 Hun Ju Lee, Candace S. Johnson, Donald Trump and Meir Wetzler Preface Remarkable advances have been made in the understanding and treatment of leukemia since its first description by Alfred Velpeau in 1827 and Alfred Donné in 1844. John Hughes Bennett gave the first official diagnosis back in 1845, and in 1856, the pathologist Rudolf Virchow coined the term leukemia from the Greek words “leukos” and “heima,” also meaning “white blood”. In 1970, it was first confirmed that some patients could be cured of leukemia, and by 1990s, the cure rate for leukemia was around 70 percent. Recent advances in the diagnosis and treatment of childhood acute lymphoblastic leukemia have since achieved a success rate of some 80 percent. This book gives a comprehensive overview of basic mechanisms underlying acute leukemia, current advances, and future directions in the management of this disease. It presents a collection of articles on acute leukemia and the most important advances made in recent years. Employing the principles of molecular biology and understanding the basic mechanisms of cell proliferation and development are essential for dealing with leukemia. The book brings together the expert knowledge from more than 40 internationally renowned scientists, and conveys the basic information, from classification, analysis and treatment, to novel molecular mechanism and principles observed in acute leukemia. It combines and assembles scientific groups worldwide dealing with acute leukemia, from the molecular to the clinical point of view. After a thorough revision of more than 30 reviews submitted, only about 50 percent were selected for the first phase of this editorial process. The book is divided in four chapters: 1) Introduction to acute leukemia, 2) Molecular mechanisms and markers, 3) Pediatric acute leukemia, and 4) Treatment and future prospects. The articles synthesize an enormous amount of scientific and clinical data and give a comprehensive overview to create state-of-the-art descriptions of acute leukemia. Objective of the book Acute Leukemia – The Scientist's Perspective and Challenge represents an extremely aggressive, malignant transformation of an early hematopoieetic precursor into an immature blast form. It may be derived from myeloid cell lines, resulting in acute myeloid leukemia (AML), or from lymphoid cell lines resulting in acute lymphoblastic leukemia (ALL). This general division has implications for different management approaches. The undifferentiated malignant X Preface clone proliferates abnormally, accumulates in bone marrow, and results in progressive hematopoietic failure with anemia, thrombocytopenia, and granulocytopenia. It may also infiltrate different organs, including liver, spleen, lymph nodes, CNS, kidneys, and gonads. Treatment options for patients with acute leukemia include chemotherapy, radiation therapy, targeted therapy, immunotherapy and stem cell or bone marrow transplantation. Finding a cure is a realistic goal for both ALL and AML, especially in younger patients. However, long-term survival is reachable in about one half of patients with acute lymphoblastic leukemia and in the minority of patients with acute myeloid leukemia. Current research, such as new genes whose protein products are suitable for targeted therapy and new strategies of immunotherapy, is focalized to improve therapy for this challenging disease. Acknowledgments Most important acknowledgements go to all the contributing authors for their assistance, eagerness, support, and their expert scientific reviews. I thank my colleagues, Lipa Cicin-Sain, Maja Matulic and Mladen Paradzik for the motivating and inspiring discussions. Thanks to my husband Darko for taking care of our children during the long days and weekends while I worked on this project, and for his understanding and encouragement. Last but not least, I am most grateful to the publishing process managers Petra Nenadic and Ana Pantar for their outstanding work, great support and indispensable help at every phase in the preparation of this book. Prof. Mariastefania Antica, PhD Rudjer Boskovic Institute, Zagreb, Croatia . ACUTE LEUKEMIA – THE SCIENTIST'S PERSPECTIVE AND CHALLENGE Edited by Mariastefania Antica Acute Leukemia – The Scientist's Perspective and Challenge. etc., and are they un-, minimally, or moderately differentiated. Acute Leukemia – The Scientist's Perspective and Challenge 4 The original classification scheme proposed by the French-American-British. in the blood smears and may be the predominant cell type. Pseudopelger–Huet and hypogranular neutrophils being most common cells are seen in M2. Acute Leukemia – The Scientist's Perspective