Myelodysplastic syndromes : from pathogenesis to diagnosis and therapy / Hamid Sayar, editor.

Format:

Book

Contributor:

Sayar, Hamid.

Series:

Recent advances in hematology research

Language:

English

Subjects (All):

Myelodysplastic syndromes.

Bone marrow--Diseases.

Bone marrow.

Physical Description:

1 online resource (309 p.)

Edition:

1st ed.

Place of Publication:

New York : Nova Science Publishers, 2013.

Language Note:

English

Summary:

In spite of tremendous advances in the field, the current understanding of pathogenesis of myelodysplastic syndromes (MDS) remains limited. Furthermore, the correct diagnosis and effective therapy of this heterogeneous group of clonal haematological disorders represent a common challenge in daily practice of haematology. This book provides a thorough, up-to-date, and comprehensive review of different aspects of MDS. Chapters are written by selected investigators and clinicians with specific expertise and track record of research in the field.

Contents:

Intro

MYELODYSPLASTIC SYNDROMES

Contents

Preface

An Introduction to Myelodysplastic Syndromes: Presentation, Diagnosis, Classification, and Prognostication

Abstract

Introduction

Etiology

Pathobiology

Cytogenetic, Genetic, and Epigenetic Alterations

Cytogenetic Abnormalities

Genetic Abnormalities

Epigenetic Abnormalities

Role of Immune System

Bone Marrow Microenvironment

Deregulated Apoptosis (Programmed Cell Death)

Clinical Presentation

Diagnosis

Bone Marrow Aspirate

Practical Technique to Assure Adequate Bone Marrow Particle Collection

Bone Marrow Biopsy

Touch Imprint and Clot Section

Flow Cytometry

Cytogenetics

Atypical Forms of MDS

MDS with Myelofibrosis

Hypoplastic MDS

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

Therapy Related MDS (t-MDS)

5q- Syndrome

Classification

Prognostication

International Prognostic Scoring System (IPSS)

WHO Prognostic Scoring System (WPSS)

MD Anderson Cancer Center (MDACC) Model

Revised IPSS (IPSS-R)

Other Prognostic Factors

Bone Marrow Fibrosis

Therapy-Related MDS (t-MDS)

Neutropania

Thrombocytopenia

References

Diagnostic Approach to Myelodysplastic Syndromes

Diagnostic Approach

Morphologic Features

Immunophenotyping by Flow Cytometry

Cytogenetic and Genetic Features

Classification of Myelodisplastic Syndromes

Refractory Cytopenia with Unilineage Dysplasia (RCUD)

Refractory Anemia with Ring Sideroblasts (RARS)

Refractory Cytopenia with Multilineage Dysplasia (RCMD)

Refractory Anemia with Excess of Blasts (RAEB)

Myelodysplastic Syndrome with Isolated del(5q)

Myelodysplastic Syndrome, Unclassifiable (MDS-U).

Myelodysplastic Syndromes with Unique Morphological Features

MDS with Fibrosis (MDS-F)

Hypoplastic MDS (h-MDS)

Erythroid-Predominant MDS (MDS-E)

Conclusion

Cytogenetic Features of Myelodysplastic Syndromes

Cytogenetic Findings

Cytogenetic Alterations and their Molecular Counterparts

Y Chromosome Loss

Rearrangements (3q)

Deletion (5q)

Rearrangements of 5q33

Partial or Total Loss of Chromosome 7: -7/del(7q)

Trisomy 8

Deletion (17p)

Deletion (20q)

Complex Karyotype

Risk Stratification of Cytogenetic Findings in MDS

Acknowledgments

Molecular Genetic Abnormalitiesin Myelodysplastic Syndromes

Mutations in Epigenetic Regulators in MDS

Mutations of the DNMT3A Gene

Mutations of the TET2 Gene

Mutations of the IDH1 and IDH2 Genes

Mutations of the EZH2 Gene

Mutations of the UTX Gene

Mutations of the ASXL1 Gene

Mutations of the c-CBL Gene

RUNX1 Mutations

RAS Mutations in MDS

TP53 Mutations

Mutations in RNA Splicing Machinery

Mutations in Other Genes in MDS Patients

Conclusion and Perspectives

Epigenetic Changes in the Pathogenesis and Therapyof Myelodysplastic Syndromes

Regulation of Gene Expression by DNA Methylation

Types of Histone Methylation Modification and Their Regulatory Mechanisms

Histone Acetylation Status

MicroRNAs and Epigenetic Machinery

Protein EVI1 and Epigenetic Machinery

Epigenetic Therapy in MDS

Azacitidine Clinical Studies

Decitabine Clinical Studies

Comparison of Azacitidine and Decitabine

Biomarkers of Sensitivity to Hypomethylating Agents

Resistance to Hypomethylating Agents

New Hypomethylating Agents.

Combinations of Hypomethylating Agents with Histone Deacetylase Inhibitors or Other Drugs

Conventional and Molecular Cytogenetic Techniques and TheirApplication in Myelodysplastic Syndromes

Work-Up at Diagnosis and Prognostic Means

Conventional Cytogenetics in MDS

CC Application in MDS

Molecular Cytogenetics in MDS

Fluorescence in-Situ Hybridization: Principle

FISH Application in MDS

FISH: Technical Considerations and Limitations

Comparative Genomic Hybridization: Principle

Array Based Karyotyping

Array-CGH: Principle and General Features

SNP-Array: Principle and General Features

Technical Considerations of Array Karyotyping

Detection of Copy Number Changes and Copy-Neutral Loss of Heterozygosity

CGH and Array-CGH: Application and Limitation in MDS

SNP-A: Application and Limitation in MDS

Next Generation Sequencing or Second Generation Sequencing (NGS)

Somatically Acquired Point Mutations in MDS

Molecular Cytogenetics Provides New Insights in MDS Pathogenesis and Progression to Acute Leukemia

Molecular Cytogenetics Insights in Tailoring Patient Management

Pathogenesis of 5q- Syndromeand Its Therapy

Possible Role of Candidate Genes from CDR in 5q- Syndrome

Role of SPARC in 5q- Syndrome

RPS14 and Ribosomopathies

Role of miR-145 and miR-146a in 5q- Syndrome

The Importance of p53 in the Molecular Mechanism of 5q- Syndrome

Activation of p53 by Ribosome Dysfunction in Model Systems

Activation of p53 and Up-Regulation of the p53 Pathway in 5q- Syndrome

Relation between p53 and miR145

Role of Other Genes in 5q- Syndrome

Role of Genes Positioned on 5q Chromosome

Role of Genes not Positioned on 5q Chromosome.

Treatment of 5q- Syndrome

Cytogenetic and Molecular Dissection of Chromosome 20 Alterations in Myelodysplastic Syndromes: Identification of Deleted and Retained Regions

Deletions of the Long Arm of Chromosome 20

Monosomy of Chromosome 20

Derivatives and Dicentrics of Chromosome 20

Isoderivatives of the Long Arm of Chromosome 20

Reciprocal Translocations Involving Chromosome 20

Commonly Deleted and Retained Regionsof Chromosome 20

Candidate Genes

Candidate Genes Present in the CDR

Candidate Genes Present in the Proximal CRR

Candidate Genes Present in the Distal CRR

The Cellular Evolutionary Entity,Epigenetic Alterations and Microenvironment of Myelodysplastic Syndromes -A Working Hypothesis of MDS Pathogenesis

The Hematopoietic Cells in MDS

The MDS Bone Marrow Cellularity

Cellular Diversity in MDS

The Clonal Origin, Evolution and Fate of MDS Cells

MDS Stem Cells in Animal Models

Molecular Changes in MDS

Alteration of Gene Expression Profile

Mutated Genes Involving Epigenetic Regulation and Reprogramming

The Microenvironment of Bone Marrow Niches and HSCs in MDS

Structural and Physiological Effects of Niches on HSC Development in the Normal Bone Marrow

Changes in Structure and Possible Effects of Niches on HSCs in MDS

Possible Role of Immune System in Development of MDS

A Working Hypothesis on Mechanism of MDS Pathogenesis

The Schema and an Overall Explanation of Our Hypothesis

Epigenetic Alterations as an Early Event in MDS Clone Formation

Effect of Environmental Niches on Regulation of Metabolism and Alteration in Epigenetics of HSCs

The Concept of MDS Stem Cell Coexistance with Normal HSCs.

Implications and Perspectives

Disclosure of Interest Conflict

Grant Support

Treatment of Lower-Risk Myelodysplastic Syndromes

Risk Stratification

MDS Patient with Anemia

Del (5q)

Immunosuppressive Therapy

Lenalidomide in Non-Del (5q) MDS

Anemic Patient Failing Less Intensive Therapies

Erythropoiesis Stimulating Agents (ESA) and Addition of Granulocyte Growth Factors

Available ESA

Lower-Risk MDS with Thrombocytopeniaor Neutropenia

Role of Granulocyte Growth Factors (GCSF and GM-CSF) for Neutropenia

Prophylactic Antibiotics in Neutropenic Patients

Prognostic Value of Thrombocytopneia

Thrombopoietin Mimetics

Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN)

Chronic Myelomonocytic Leukemia (CMML)

Iron Overload

Immunosuppression

Anti-Thymocyte Globulin (ATG) Single Agent

Cyclosporine Single Agent

Combination of ATG and Cyclosporine

Summary

Treatment of Higher-Risk Myelodysplastic Syndromes

Lower-Risk MDS that are Treated Similar to Higher-Risk Disease

Higher-Risk MDS

Evaluation of Response in Patients with MDS: The IWG Response Criteria

DNA Hypomethylating Agents

Azacitidine

Decitabine

Azacitidine Versus Decitabine

Route, Scheduling, Dosing and Duration of Treatment

Toxicities and Adverse Events

Sequential Treatment with Hypomethylating Agents

Hypomethylating Agents in Low Risk MDS

Hypomethylating Agents in Poor-Risk Cytogenetics

TET-2 Mutations and Response to Hypomethylating Agents

Hypomethylating Agents in the Elderly

Outcomes after Failure of Hypomethylating Agents

High Intensity (Induction) Chemotherapy.

Hematopoietic Stem Cell Transplantation (HSCT).

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

Description based on print version record.

ISBN:

1-62417-580-5

OCLC:

923668409