1;List of Contents;5 2;List of Contributors;7 3;APL as a Paradigm in Biomedical Research: A Journey Toward the Cure;8 4;Mouse Models of Acute Promyelocytic Leukemia;10 4.1;1 Models;11 4.2;2 Cooperating Events;18 4.3;3 Pathogenesis, Conclusions;21 4.4;4 Immune Modulation of APL;22 4.5;5 Therapies;23 4.6;6 Arsenic Trioxide;25 4.7;7 Histone Deacetylase Inhibitors;29 4.8;8 Additional Investigational Therapies;30 4.9;9 Therapy, Conclusions;31 4.10;10 Perspectives;31 4.11;References;32 5;The PLZF Gene of t(11;17)-Associated APL;38 5.1;Summary;49 5.2;References;49 6;SUMO, the Three Rs and Cancer;56 6.1;1 Introduction;56 6.2;2 At the Chromosomal Level;58 6.3;3 DNA Replication and Repair;64 6.4;4 SUMO and Cancer: Caretakers and Gatekeepers;66 6.5;5 Conclusion;70 6.6;References;71 7;Emerging Role for MicroRNAs in Acute Promyelocytic Leukemia;80 7.1;1 Introduction;81 7.2;2 microRNAs;82 7.3;3 microRNAs and Hematopoietic Lineage Specificity;84 7.4;4 Regulation of miR-223 Expression Levels in Acute Promyelocytic Leukemia;85 7.5;5 C/EBPa and NFI- A;86 7.6;6 miR-223 Upstream Region;88 7.7;7 Concluding Remarks;89 7.8;References;90 8;The Theory of APL Revisited;92 8.1;1 Introduction;93 8.2;2 The Fusion Proteins of APL Are Oncogenes of the Early Myeloid Hematopoietic Compartment;94 8.3;3 X-RARa Proteins Are Necessary but Not Sufficient to Cause Leukemia and Represent Biologically Distinct RARa Mutants;95 8.4;4 RARa- X Proteins Do Play a Critical Role in APL Leukemogenesis, but Are Not Sufficient for Full- Blown Transformation;95 8.5;5 Multiple Genetic Hits in APL Pathogenesis;96 8.6;6 XMolecules Are Involved in the Control of the Cell Mitogenic and Survival Signals, and of Genomic Stability;97 8.7;7 The Crosstalk Between X and RAR/RXR Pathways;98 8.8;8 X Haploinsufficiency and Functional Interference of X-RARa and RARa- X with X- Regulated Pathways Is Critical for APL Leukemogenesis;99 8.9;9 The X Moiety Lends to the X-RARa Fusion Protein Distinct Gain- of- Function Proteins;100 8.10;10 Conclusions and Future Directions;100 8.11;References;103 9;Treatment of Acute Promyelocytic Leukemia by Retinoids;108 9.1;1 Background: Results of Chemotherapy Alone in APL;110 9.2;2 First Results Obtained with ATRA Alone in APL;112 9.3;3 ATRA Combined to Intensive Chemotherapy in Newly Diagnosed APL;113 9.4;4 Consolidation and Maintenance Treatment with ATRA in APL;114 9.5;5 Prognostic Factors in Patients Treated with ATRA and Chemotherapy;115 9.6;6 Unresolved Issues in the ATRA and Chemotherapy Combination Treatment of Newly Diagnosed APL;118 9.7;7 Role of Retinoids in the Treatment of Relapsing APL;120 9.8;8 APL Differentiation Syndrome (ATRA Syndrome) and Other Side Effects of ATRA;121 9.9;References;125 10;Arsenic Trioxide and Acute Promyelocytic Leukemia: Clinical and Biological;136 10.1;1 As2O3 as Single Treatment in Remission Induction;137 10.2;2 Dosage and Pharmacokinetics;137 10.3;3 As2O3 as Combined Treatment with ATRA in Remission Induction;140 10.4;4 Adverse Effects;141 10.5;5 Postremission Treatment and Survival Time;142 10.6;6 Molecular Mechanisms of Arsenic Action;143 10.7;7 Perspectives;146 10.8;References;147 11;Front Line Clinical Trials and Minimal Residual Disease Monitoring in Acute Promyelocytic Leukemia;152 11.1;1 Diagnostic Approach;153 11.2;2 Molecular Architecture of the t(15;17) and Definition of the RT- PCR Strategy;154 11.3;3 Technical Issues Related to RT-PCR Amplification;155 11.4;4 Strategies to Improve RT-PCR Monitoring and Quantitative Real- Time RT- PCR;156 11.5;5 Front-Line Therapy;157 11.6;References;160 12;Histone Deacetylase Inhibitors in APL and Beyond;164 12.1;1 Cancer Epigenetics and Histone Acetylation;165 12.2;2 The Histone Deacetylase Family;168 12.3;3 Histone Deacetylase Inhibitors;174 12.4;4 Future Directions;184 12.5;References;189 13;Monoclonal Antibody Therapy of APL;212 13.1;1 Introduction;212 13.2;2 Background;213 13.3;3 Therapies;216 13.4;4 Conclusion;221 13.5;References;222 14;Targeting APL Fusion Proteins b