Epigenetics and Proteomics of Leukemia : A Synergy of Experimental Biology and Computational Informatics

This book reviews the current state of epigenetics and proteomics of leukemia and introduces the methods that are important to process and evaluate these factors in leukemia. In particular, epigenetic modifiers and their inhibitors in leukemia treatment as well as approaches to the epigenetic treatment of leukemia are covered. Various computational methods for proteome analysis are also described in detail, including 2DE fractionation and visualization, proteomic data processing, image acquisition and data anlaysis, and more. Protein localization in leukemia is also covered, in addition to the future of leukemia therapy. Epigenetics and Proteomics of Leukemia is an ideal book for advanced biomedical scientists and students, medical doctors and students, bioinformatics and health informatics researchers, computational biologists, structural biologists, systems biologists, and bioengineers. Preface Introduction The Authors' Publications Are Presented in the Monograph Contents Notations Text Parts Symbols Operators Abbreviations List of Figures List of Tables Part I Epigenetics in Leukemia 1 Epigenetic and Genetic Alterations in Leukemia 1.1 Hematopoiesis 1.2 Types of Leukemia 1.2.1 Chronic Leukemia 1.2.2 Acute Leukemia 1.3 Genetic Landscape of Leukemia 1.4 Epigenetic Landscape of Leukemia 1.4.1 Changes in Methylation in Carcinogenesis 1.4.2 Histone Modifications 1.4.3 Interaction of DNA and Histone Modifications 1.5 Treatment of Leukemia 1.5.1 Standard Treatment of AML 1.5.2 Strategies to Improve Remission Induction References 2 Epigenetic Modifiers and Their Inhibitors in Leukemia Treatment 2.1 In vitro Studies of ATRA Effects on APL Cells 2.2 Effects of ATRA Combination with Nucleotide Analogues and Ionizing Radiation 2.3 Role of Protein Kinases and Their Inhibitors During Leukemic Cell Differentiation 2.4 Etoposide and Z-VAD(OH)-FMK Effects on AML Cells 2.5 Enhanced Effect of Epigenetic Modifiers on APL Cell Proliferation and Death 2.6 Effects of Vitamin B3 and Phenylbutyrate on APL Cells 2.7 Sodium Butyrate and Trichostatin A Impact on Granulocytic Differentiation of APL Cells 2.8 Combination of BML-210 and ATRA Induce Granulocytic Differentiation of APL Cells 2.9 Potential Histone Deacetylase Inhibitor FK228 2.10 Combined Effect of Belinostat, ATRA, and 3-deazaneplanocin A on AML Cells 2.11 Histone Methylation Inhibition Benefits to APL Differentiation 2.12 DNMT Inhibitors Contribution Toward Leukemia Cell Granulocytic Differentiation 2.12.1 Effects of DNA Methyltransferase Inhibitor Zebularine on APL Cells 2.12.2 Procaine, Decitabine, and All-Trans Retinoic Acid Treatment Cause APL Cell Differentiation 2.12.3 DNA Methyltransferase Inhibitor RG108 Has Anti-proliferative Effect on APL Cells 2.13 Promising Benefits on Antileukemic Effect Demonstrate EGCG References 3 Chromatin Remodeling During Leukemia Cell Proliferation and Differentiation 3.1 Chromatin Functional Regulation by Histone Modifications 3.1.1 HDAC Inhibitor BML-210 Affects Leukemia Cells via Chromatin Remodeling 3.1.2 Histone Modifications Initiated by HDACi Phenylbutyrate and Vitamin B3 3.1.3 HDAC Inhibitor FK228 Induces Antileukemic Effects via Changes in Histone Modifications 3.1.4 Belinostat Effects on Epigenetic Changes in Leukemia Cells and Promotes Differentiation 3.1.5 Combined Epigenetic Treatment Promotes Conventional Leukemia Cell Differentiation 3.1.6 Combined Epigenetic Treatment in Leukemia Xenograft Model 3.1.7 HMT Inhibitor BIX-01294 Effects on Epigenetic Changes of DNA and Proteins 3.1.8 Multifunctional Epigallocatechin Gallate Reduces Leukemia Cell Growth and Induces Apoptosis 3.2 DNA Methylation and Epigenetic Regulation 3.2.1 Procaine Effects on Epigenetic Changes of DNA and Proteins 3.2.2 DNMT Inhibitors, RG108 and Zebularine Effects on Epigenetic Changes of DNA and Proteins References Part II Proteomics in Leukemia 4 Proteome in Leukemic vs.=1000 Differentiated Leukemia Cells 4.1 Proteomic Analysis of Cytoplasmic and Nuclear Proteins in Human Hematopoietic CD34+, AML Cell Line KG1 and Mature Neutrophils 4.2 Proteomic Analysis of APL Cells Induced to Differentiation 4.3 Proteome Profile in APL Cells Induced with Histone Deacetylase Inhibitor BML-210 4.4 HDAC Inhibitor Belinostat Modulates Protein Profile in NB4 Cells 4.5 Proteomic Maps of Leukemia Cells Induced to Granulocytic Differentiation and Apoptosis References 5 Protein Phosphorylation in Leukemia 5.1 Tyrosine Phosphorylation of Cytosolic Proteins during Differentiation of Leukemic Cells 5.2 Tyrosine Phosphorylation of Nuclear and Cytosolic Proteins in Differentiated and Apoptotic AML Cells 5.3 Role of Dystrobrevin-α in Leukemia Cells During Proliferation and Differentiation 5.4 Dystrobrevin-α in Proliferating, Differentiated and Apoptotic Leukemia Cells 5.5 Dystrobrevin-α in Induced to Apoptosis Leukemia Cells References 6 Computational Methods for Proteome Analysis 6.1 Automatic 2DEG Image Analysis 6.1.1 2DEG Image Analysis Automation Problem 6.1.1.1 Aims and Significance 6.1.1.2 Strategies of Analysis 6.1.1.3 Challenges 6.1.2 Solution Ways of Automation Problem 6.1.3 Requirements for Automatic Analysis System 6.1.4 2DEG Image Matching Modeling 6.1.5 Requirements for 2DEG Image Matching Model 6.1.6 Automatization of 2DEG Image Analysis 6.2 2DEG Image Matching 6.2.1 Specification of 2DEG Image Matching 6.2.2 Preparation of Individual 2DEG Images 6.2.3 Initial 2DEG Image Matching 6.2.3.1 Estimation of Key Points and Regions 6.2.3.2 Control of Errors During the Search of Matching Areas 6.2.3.3 First Algorithm for the Search of Matching Areas 6.2.3.4 Second Algorithm for the Search of Matching Areas 6.2.3.5 Development of ` =9 [abbreviations]MLP Detector for Area Similarity Estimation Subsection Generalization 6.2.3.6 Third Algorithm for the Search of Matching Areas 6.2.4 Final 2DEG Image Matching 6.2.4.1 Geometrical Transformation of 2DEG Image 6.2.4.2 Experimental Evaluation of the Final 2DEG Image Matching 6.3 Proteomic Data Analysis 6.3.1 Segmentation of 2DEG Images 6.3.1.1 First Algorithm for 2DEG Image Segmentation 6.3.1.2 Second Algorithm for 2DEG Image Segmentation 6.3.2 Models of Protein Spots and Modeling 6.3.2.1 Common Protein Spot Models 6.3.2.2 Need for Complex Protein Spot Models 6.3.2.3 Gaussian-Based Complex Models 6.3.2.4 Spline-Based (-Shaped) Models 6.3.2.5 Bell-Shaped Function-Based Models 6.3.2.6 Sigmoid-Based Models 6.3.2.7 Protein Spot Modeling 6.3.2.8 Experimental Comparison of Spot Models 6.3.3 Protein Spot Parametrization 6.3.3.1 Estimation of Protein pI and MW Values 6.3.3.2 Estimation of Protein Quantity Changes References Part III Protein Localization in Leukemia 7 Protein Translocation into the Nucleus during Leukemia Cell Differentiation 7.1 Method for Protein Translocation Assay from Cytosol into the Nucleus 7.2 Translocation of Transcription Regulators into the Nucleus 7.3 Dystrobrevin-γ Translocation into the Nucleus of Acute Promyelocytic Leukemia Cells References 8 Protein Visualization in Leukemia Cells 8.1 Comparative Analysis of Histones during Granulocytic Differentiation 8.2 Visualization of Dystrobrevin-α in Leukemia Cells 8.3 Dystrobrevin-α Localization in Leukemia Cells Induced to Apoptosis References 9 Computational Methods for Protein Localization Analysis 9.1 Overview of Typical Workflow of Automated Fluorescence Image Analysis 9.1.1 Fluorescence Image Acquisition 9.1.2 Image Preparation 9.1.3 Image Analysis 9.1.3.1 Nuclei Segmentation 9.1.3.2 Cell Segmentation 9.1.3.3 Image Postprocessing 9.1.4 Data analysis 9.2 Automatic Protein Localization in Fluorescence Images of Blood Cells 9.2.1 Fluorescence Image Acquisition Setup 9.2.2 Image Preparation 9.2.3 Nuclei Detection and Segmentation 9.2.4 Cell Segmentation 9.2.5 Image Postprocessing 9.2.6 Data Analysis and Visualization References Future Therapy in Leukemia Future Therapy in Leukemia References A Clinical Trials of Drugs for Leukemia Drugs for Chronic Lymphocytic Leukemia Drugs for Chronic Myeloid Leukemia Drugs for Acute Lymphocytic Leukemia Drugs for Acute Myeloid Leukemia B Cell Lines Used in Study References C Chemical Agents Used in the Studies References D Identified and Associated into Interactome Proteins E Identified Proteins in NB4 Cells Index