Hematopathology

Morphology, Immunophenotype, Cytogenetics, and Molecular Approaches

Faramarz Naeim, P. Nagesh Rao, Wayne W. Grody

• Publisher: Academic Press
• Year: 2009
• eBook ISBN: 9780080919485
• Topic: Sciences biologiques
• Subtopic: Anatomie humaine et physiologie

This comprehensive, full color hematopathology reference book emphasizes immunophenotpic features, cytogenetic studies, and diagnostic molecular aspects. Hematopathology begins with introductions to morphologic evaluation of the hematopoietic tissues and principles of immunophenotyping, cytogenetics and molecular studies followed by chapters dedicated to different types of hematologic disorders. Each chapter starts with a basic overview of hematopathlogy followed by a comprehensive review of immunophenotypic, cytogenetic and molecular findings. The text is balanced with large numbers of full color images, graphs, charts, and tables to assist the reader in understanding these highly technical issues.- Emphasizes the immunophenotypic features, cytogenetic studies, and diagnostic molecular aspects of hematology- Features hundreds of images, charts and tables for the identification of hematologic disorders not only based on histopathologic features, but also with the use of advanced accessory techniques

Chapter 1. Structure and Function of Hematopoietic Tissues

Bone Marrow Structure and Function

Bone marrow is a mesenchymal-derived complex structure consisting of hematopoietic precursors and a complex microenvironment that facilitates the maintenance of hematopoietic stem cells (HSCs) and supports the differentiation and maturation of the progenitors. All differentiated hematopoietic cells including lymphocytes, erythrocytes, granulocytes, macrophages, and platelets are derived from HSCs.

In the early embryonic life, HSCs first appear in yolk sac and mesodermal tissue of the aorta-gonad-mesonephros region [1–3]. These stem cells then migrate and colonize in a series of early hematopoietic sites including liver, thymus, spleen, and omentum [1–3]. They eventually reside in bone marrow as their permanent home, where they give rise to sequential generations of blood cells throughout adult life. Stem cells have highly specific homing properties, demonstrate very high self-renewal potential, and are capable of differentiation. They share morphologic features of blast cells but are distinguished by their functional properties, such as various colony-forming units (CFUs) and expression of certain differentiation-associated macromolecules. The most primitive (pluripotent) HSCs express CD34 and are negative for CD38 and HLA-DR [4–6]. These primitive cells, which include long-term repopulating stem cells, are also characterized by low level expression of c-kit receptor (CD117) and absence of lineage specific maturation markers. There is a spectrum of heterogeneity in the bone marrow stem cell pool: a continuum of cells with decreasing capacity for self-renewal and increasing potential for differentiation. This trend is also associated with changes in immunophenotypic features. For example, the committed stem cells (short-term repopulating cells), in addition to CD34, appear to express CD38 and/or HLA-DR. The pluripotent HSCs comprise about 1 per 20,000 of bone marrow cells, and only a small fraction of them are active, whereas the remaining majority are in a “resting” phase, on call for action when it is necessary [5–7]. Based on the “clonal succession” hypothesis, a series of stem cells successively contribute to the clonal expansion to maintain a balanced hematopoiesis throughout life [8–10].

The choice of the bone marrow stem cells between self-renewal and differentiation appears to be stochastic, meaning that the commitment of a stem cell to self-renewal or to a particular pair of progeny of given differential potential is a random event and follows the probability rules of statistics [11–13]. In this random process, activation of certain complex nuclear transcription factors appears to play an important role.

Similar to the hematopietic cells, bone marrow stromal cells are derived from pluripotent stem cells [14–16]. In other words, two separate and distinct pluripotent stem cells are simultaneously at work in bone marrow: hematopoietic and stromal. These two systems not only co-exist but closely interact with each other. Stromal cells are composed of a heterogeneous cell population including adipocytes, fibroblast-like cells, endothelial cells, and osteoblasts [17–20]. They produce a number of cytokines and a group of proteins that are involved in facilitating cell–cell interactions and presenting the cytokines and growth factors to the hematopoietic progenitor cells (Table 1.1). Stromal cells with their extracellular matrix make a mesh of fibrovascular environment to home and support the hematopoietic precursors [20–25]. The thin-walled venous sinuses are the most prominent vascular spaces in the bone marrow. They consist of an inside layer of endothelial cells supported by an outer layer of fibroblast-like (parasinal, adventitial) stromal cells. They receive blood from the branches of the nutrient artery and periosteal capillary network. The nutrient artery penetrates the bony shaft, branches into the bone marrow cavity, and forms capillary–venous sinus junctions [26, 27]. The periosteal capillary network connects with the sinuses at the bone marrow junction through the Haversian canals. The smaller venous sinuses drain into larger centrally located sinuses, which connect together to form the comitant vein. The comitant vein and the nutrient artery run through the bone marrow cavity adjacent to one another in the same vascular canal (Figure 1.1).

Table 1.1. The main adhesion molecule families.

...

Adhesion molecule families	Major distribution	Ligand/matrix
(a) Leukocyte cell adhesion molecules (Leu CAM)
CD11a (LFA-1α)	Leukocytes	ICAM-1
CD11b (MAC-1)	Neutrophils, monocytes	C3bi, ICAM-1
CD11c (gp150/95)	Granulocytes, monocytes	C3bi
CD18 (LFA-1β)	Widespread	CD11a, b, c
(b) Immunoglobulin superfamily
CD2 (LFA-2)	T lymphocytes	LFA-3
CD50 (ICAM-3)	Leukocytes	LFA-1
CD58 (LFA-3)	Widespread	CD2
CD54 (ICAM-1)	Widespread	LFA-1
CD102 (ICAM-2)	Endothelial cells	LFA-1
CD106 (VCAM-1)	Dendritic cells, endothelial cells	VLA-4
ICAM-4	Erythroid	AlphaVbeta3
(c) Selectins

Table of contents

• Brief Table of Contents
• Table of Contents
• List of Figures
• List of Tables
• Copyright Page
• Dedication
• Preface
• Acknowledgements
• List of Contributors
• Chapter 1. Structure and Function of Hematopoietic Tissues
• BibliographyReferences
• Chapter 2. Principles of Immunophenotyping
• BibliographyReferences
• Chapter 3. Principles of Cytogenetics
• BibliographyReferences
• Chapter 4. Principles of Molecular Techniques
• BibliographyReferences
• Chapter 5. Morphology of Abnormal Bone Marrow
• BibliographyReferences
• Chapter 6. Reactive Lymphadenopathies
• BibliographyReferences
• Chapter 7. Bone Marrow Aplasia
• BibliographyReferences
• Chapter 8. Myelodysplastic Syndromes
• BibliographyReferences
• Chapter 9. Chronic Myeloproliferative Diseases
• BibliographyReferences
• Chapter 10. Myelodysplastic/Myeloproliferative Diseases
• BibliographyReferences
• Chapter 11. Acute Myeloid Leukemia
• BibliographyReferences
• Chapter 12. The Neoplasms of Precursor Lymphoblasts
• BibliographyReferences
• Chapter 13. Acute Leukemias of Ambiguous Lineage
• BibliographyReferences
• Chapter 14. Lymphoid Malignancies of Non-precursor Cells
• BibliographyReferences
• Chapter 15. Mature B-Cell Neoplasms
• BibliographyReferences
• Chapter 16. Plasma Cell Myeloma and Related Disorders
• BibliographyReferences
• Chapter 17. Mature T-Cell and NK-Cell Neoplasms
• BibliographyReferences
• Chapter 18. Hodgkin Lymphoma
• BibliographyReferences
• Chapter 19. Non-neoplastic and Borderline Lymphocytic Disorders
• BibliographyReferences
• Chapter 20. Mastocytosis
• BibliographyReferences
• Chapter 21. Histiocytic and Dendritic Cell Disorders
• BibliographyReference
• Chapter 22. Granulocytic Disorders
• BibliographyReference
• Chapter 23. Disorder of Red Blood Cells: Anemias
• BibliographyReferences
• Chapter 24. Disorders of Megakaryocytes and Platelets
• BibliographyReferences