HEMATOLOGY – SCIENCE AND PRACTICE Edited by Charles H. Lawrie Hematology – Science and Practice Edited by Charles H. Lawrie Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 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 Sandra Bakic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 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 Hematology – Science and Practice, Edited by Charles H. Lawrie p. cm. ISBN 978-953-51-0174-1 Contents Preface IX Part 1 Blood Physiology 1 Chapter 1 Mechanisms Controlling Hematopoiesis 3 Katja Fiedler and Cornelia Brunner Chapter 2 Negative Regulation of Haematopoiesis: Role of Inhibitory Adaptors 47 Laura Velazquez Chapter 3 The Role of EMT Modulators in Hematopoiesis and Leukemic Transformation 101 Goossens Steven and Haigh J. Jody Chapter 4 Asymmetric Division in the Immuno-Hematopoietic System 121 Daniel Jimenez-Teja, Nadia Martin-Blanco and Matilde Canelles Chapter 5 Nitric Oxide / Cyclic Nucleotide Regulation of Globin Genes in Erythropoiesis 135 Vladan P. Čokić, Bojana B. Beleslin-Čokić, Gordana Jovčić, Raj K. Puri and Alan N. Schechter Chapter 6 Mechanisms of αIIbβ3 Biogenesis in the Megakaryocyte: A Proteomics Approach 171 Amanda Chen, Haiqiang Yu, Haiteng Deng and W. Beau Mitchell Chapter 7 SATB1: Key Regulator of T Cell Development and Differentiation 195 Kamalvishnu P. Gottimukkala, Mithila Burute and Sanjeev Galande Chapter 8 Neutrophil Chemotaxis and Polarization: When Asymmetry Means Movement 211 Doris Cerecedo VI Contents Chapter 9 Intravascular Leukocyte Chemotaxis: The Rules of Attraction 229 Sara Massena and Mia Phillipson Chapter 10 Membrane Trafficking and Endothelial-Cell Dynamics During Angiogenesis 253 Ajit Tiwari, Jae-Joon Jung, Shivangi M. Inamdar and Amit Choudhury Part 2 Hematological Pathologies 281 Chapter 11 Translational Control in Myeloid Disease 283 Nirmalee Abayasekara and Arati Khanna-Gupta Chapter 12 Molecular Mechanisms in Philadelphia Negative Myeloproliferative Neoplasia 299 Ciro Roberto Rinaldi, Ana Crisan and Paola Rinaldi Chapter 13 Physiological and Pathological Aspects of Human NK Cells 337 Chiara Vitale, Renato Zambello, Mirna Balsamo, Maria Cristina Mingari and Massimo Vitale Chapter 14 Stratification of Patients with Follicular Lymphoma 371 Hasan A. Abd El-Ghaffar, Sameh Shamaa, Nadia Attwan, Tarek E. Selim, Nashwa K. Abosamra, Dalia Salem, Sherin M. Abd El-Aziz and Layla M. Tharwat Chapter 15 MicroRNA Expression in Follicular Lymphoma 393 Charles H. Lawrie Chapter 16 Epstein-Barr Virus-Encoded miRNAs in Epstein-Barr Virus-Related Malignancy 409 Jun Lu, Bidisha Chanda and Ai Kotani Chapter 17 Animal Models of Lymphoproliferative Disorders Focusing on Waldenström’s Macroglobulinemia 425 Anastasia S. Tsingotjidou Chapter 18 Systemic Mastocytosis: An Intriguing Disorder 467 Antonia Rotolo, Ubaldo Familiari, Paolo Nicoli, Daniela Cilloni, Giuseppe Saglio and Angelo Guerrasio Part 3 Hematology in the Clinic 487 Chapter 19 Targeting the Minimal Residual Disease in Acute Myeloid Leukemia: The Role of Adoptive Immunotherapy with Natural Killer Cells and Antigen-Specific Vaccination 489 Sarah Parisi and Antonio Curti Contents VII Chapter 20 The Ubiquitin-Proteasomal System and Blood Cancer Therapy 497 Xinliang Mao and Biyin Cao Chapter 21 Heparin-Induced Thrombocytopenia 517 Kazuo Nakamura Chapter 22 Converting Hematology Based Data into an Inferential Interpretation 541 Larry H. Bernstein, Gil David, James Rucinski and Ronald R. Coifman Chapter 23 The Effects of Splenectomy and Autologous Spleen Transplantation on Complete Blood Count and Cell Morphology in a Porcine Model 553 Nina Poljičak-Milas, Anja Vujnović, Josipa Migić, Dražen Vnuk and Matko Kardum Chapter 24 Physiological Factors in the Interpretation of Equine Hematological Profile 573 K. Satué, A. Hernández and A. Muñoz Preface ‘Blood, blood, glorious blood, Thicker than water and nicer than mud’ Humphrey Kay - The Hematologist’s Song Hematology encompasses the physiology and pathology of blood and of the blood- forming organs. In common with other areas of medicine, the pace of change in hematology has been breathtaking over recent years. There is now a plethora of treatment options available to the hematologist which happily coincides with a greatly improved outlook for the vast majority of patients with blood disorders, in particular those with hematological malignancies. Improvements in the clinic reflect, and in many respects are driven by, advances in our scientific understanding of hematological processes under both normal and disease conditions. This book which consists of a selection of essays aims to inform both specialist and non-specialist readers about some of the latest advances in hematology, in both laboratory and clinic. The first section of this book (Section 1 - Blood Physiology) is concerned with the study of the molecular and cellular mechanisms behind the physiological functioning of the blood system. The first three chapters deal with the mechanisms behind early hematopoiesis, the process occurring almost exclusively in the bone marrow by which all mature blood cells are generated from multi-potent hematopoietic stem cells (HSCs). This is a finely balanced process that is tightly controlled by a complex network of inter-related signaling pathways and molecular components. In Chapter 1, Fiedler and Brunner review some of the intricate regulatory mechanisms involved in this process, in particular focusing on the role of transcription factors in early lineage control and lineage commitment. In Chapter 2, Velazquez describes the role that negative regulation plays in hematopoiesis, and in particular the function of members of the inhibitory adaptor family such as DOK, Lnk and SOCS, their role in cytokine signaling pathways and hematological pathologies. This chapter also explores the potential therapeutic use of these inhibitors and associated regulators. Expanding upon the theme of hematopoiesis, Goossens and Jody, in Chapter 3, discuss the role of modulators of the epithelial to mesenchymal transition (EMT) pathway focusing on the function of SNAI family members, snail and slug, and interestingly how they can be involved in leukemic transformation. X Preface The ability of the HSC (and other cells along the hematopoietic pathway) to divide into two functionally distinct daughter cells, one that is differentiated whilst the other retains self-renewal properties and can continue to proliferate, is crucial to the maintenance of the hematopoietic system. So-called asymmetric division is discussed in Chapter 4 by Jimenez-Teja et al. The authors outline the historical perspective behind this field before going into a detailed review of the function of asymmetric division in both hematopoietic and immune systems, as well as the latest evidence to suggest that asymmetric division and in particular abnormal functioning of cell fate determinant molecules can lead to cancer. After the initial commitment step the HSC loses its ability to self-renew and the hematopoietic pathway bifurcates with formation of either the common lymphoid progenitor (CLP) or common myeloid-erythroid progenitor (CMEP) cells. CLPs can give rise to mature NK, B and T cells, whilst the CMEPs can form erythrocyte, megakaryocyte, granulocyte and monocyte populations. In Chapter 5, Čokić et al. describe the role of nitric oxide/cyclic nucleotide regulation in erythropoiesis, the formation of red blood cells (erythrocytes). In this chapter the authors provide an overview of the erythropoietic pathway including the crucial role that GATA1/2 plays in hemoglobin switching. They present some novel findings whereby they used microarrays to measure changes in expression levels of globin-related genes during ontogenesis, and later on provide evidence to show that NO and cGMP can induce globin gene expression. Platelets play an essential role in hemostasis and thrombosis, initiating clot formation in response to cellular damage. Central to the clotting process is platelet aggregation mediated by the cross-linking of intergrin αIIbβ3 to fibrinogen, von Willebrand factor and other soluble ligands. Aside from their role in physiological processes, platelets may also form pathological thrombi which can lead to myocardial infarction or stroke. Therefore inhibitors of αIIbβ3 are of great clinical interest. In Chapter 6, Chen et al. use a proteomic approach to identify binding partners to αIIb and the αIIbβ3 heterodimer expressed in cord-blood derived megakaryocytes. Using this technique they identified and validated DNAJC10 as a novel binding partner of the immature form of αIIbβ3, and showed that it binds early on in the biogenic pathway. Furthermore, the authors found that silencing of DNAJC10 could modulate levels of αIIbβ3 in megakaryocytes as well as HEK293 cells transfected with aIIb and b3 cDNA constructs. Chapter 7 by Gottimukkala, Burute and Galande concerns the role of the transcription factor SATB1 in the development and differentiation of T-cells, in particular, the key role that this molecule plays in T H differentiation. The authors also describe how the loss of SATB1 function may be associated with the T-cell lymphoma, Sézary syndrome. Cell polarization is necessary for the migration of cells in many processes including embryogenesis, inflammation and tumor metastasis. Chemoattractant recruitment of neutrophils to trauma sites is an essential process of the inflammatory response. [...]... only give rise to pDC and mDC (Geissmann et al., 2010; Naik et al., 2007; Onai et al., 2007) Besides the characterization of MDP and CDP by several studies, further progenitor populations for eosinophils, basophils and mast cells have been isolated downstream of the GMP and their position in the hematopoietic hierarchy is depicted in Figure 1 Moreover, 6 Hematology – Science and Practice Fig 1 Model... antigen exposure is regulated by key transcription factors (bold) that activate cell-specific genes and mutually repress transcription factors necessary for alternative cell differentiation 16 Hematology – Science and Practice In B cells, the lineage commitment and the maintenance of the B cell fate throughout B cell development is achieved by a single transcription factor – Pax5 (Cobaleda et al., 2007;... Preface In summary, these essays cover a wide range of subjects pertaining to hematology, both theoretical and clinical, and aptly illustrate both the complexity and challenges that face the hematologist today and in the future This book is dedicated to my wonderful and understanding wife María, and my two beautiful children, Julia and Carlos Special thanks should also be given to Dr Chris Hatton (Director... macrophages as well as dendritic cells and involves again the selection of specific gene expression programs to 12 Hematology – Science and Practice Fig 3 Terminal granulopoiesis in the bone marrow The terminal granulopoiesis that is characterized by sequential formation of different granule types and segmentation of the nucleus starts at the myeloblast/promyelocyte stage and ends with mature neutrophils... the pre-BCR signaling by promoting the V to DJ recombination at the IgH locus (Nutt, S L et al., 1997) and also by regulating directly the expression of the signaling molecule BLNK (Schebesta et al., 2002) Additionally, Pax5 is essential for the upregulation of CD19 and Iggene expression (Kozmik et al., 1992; Nutt, S L et al., 1997) Pax5-deficient 14 Hematology – Science and Practice B cells are arrested... hematopoiesis and takes place primarily in the bone marrow, where few hematopoietic stem cells give rise to a differentiated progeny following a series of more or less well-defined steps of multipotent progenitors and lineage-restricted 4 Hematology – Science and Practice precursors leading to a hierarchical structure of the process During the course of hematopoiesis cells lose their proliferative potential... differentiation pathways by blocking Blimp1 (Johnston et al., 2009) In the periphery, CD4+ effector T cells can be converted by exposure to TGF and IL-2 to inducible regulatory T cells (iTregs) expressing CD25 at the surface and, like nTregs, FoxP3 as a master transcription factor necessary for Treg function (Davidson et al., 2007; Zheng et al., 2007) (Figure 7) 20 Hematology – Science and Practice Fig 7 Terminal... multipotent progenitors with myelolymphoid or myelo-erythroid potential, such as the lymphoid-primed multipotent progenitor (LMPP) (Iwasaki & Akashi, 2007) Additionally, a lot of research concerning prospective isolation and characterization of HSC and multipotent progenitors has provided insight into the surface marker expression on these types of cells leading to the definition of HSC and multipotent... phenotype characterized by the production of large amounts of IFN, IL-2 and TNF TH1 cells mediate the defense against infections by intracellular microbes and the isotype switching to IgG2a and IgG2b In contrast, TH2 cells are generated in the presence of IL-4 and also secrete, depending on the upregulation of the transcription factor GATA-3, IL-4 together with IL-5 and IL-13 Thereby, humoral responses... parasites and extracellular pathogens are supported and also the class switching to IgG1 and IgE (Mosmann et al., 1986; Mowen & Glimcher, 2004; Szabo et al., 2003) A third TH subpopulation was described, the TH17 cells that is characterized by the secretion mainly of IL-17A and IL17F, but also IL-21 and IL-22, protecting the host against bacterial and fungal infections Their differentiation is induced by . HEMATOLOGY – SCIENCE AND PRACTICE Edited by Charles H. Lawrie Hematology – Science and Practice Edited by Charles H. Lawrie. Thicker than water and nicer than mud’ Humphrey Kay - The Hematologist’s Song Hematology encompasses the physiology and pathology of blood and of the