Description
This book provides an unprecedented overview of “Targeted Therapies” for acute myeloid leukemias. It aims at an almost comprehensive coverage of the diverse therapeutic strategies that have been developed during the last decade and are now being evaluated in early clinical trials. Paired and authoritative chapters by leading research scientists and clinicians explain basic concepts and clinical translation of topics that include the underlying genetic and proteomic abnormalities of AML, the development of novel nucleoside analogues, the roles of microRNAs, apoptosis regulators Bcl-2 and p53 and of critical cell signaling proteins such as PIM, FLT3, Raf/MEK, PI3K/AKT/mTOR and aurora kinases. Chapters on epigenetic mechanisms, nuclear receptors, cell surface antigens, the hypoxic leukemia microenvironment, stem cells and leukemia metabolism provide insights into leukemia cell vulnerabilities. Cell therapies utilizing T-, NK- and mesenchymal stem cells and progress in hematopoietic transplantation strategies round up this overview of the multi-dimensional therapeutic landscape in which leukemia specialists develop treatment strategies that are expected to make “leukemia history” in the near future. 1. Introduction/Perspective Michael Andreeff 2. Genetics and Classification of Acute Myeloid Leukemia Alison R. Walker and Guido Marcucci: 3. Proteomics of AML to guide Selection of Therapy Steven M. Kornblau Part I: Apoptosis 4. Roles of Apoptosis Regulating Bcl-2-Family Genes in AML John C. Reed 5. Bcl-2 family: Translational aspects Prithviraj Bose and Steven Grant 6. IAP Family and Proteins as Therapeutic Targets for Acute Myeloid Leukemia Bing Carter and Michael Andreeff 7. TP53 Mutations in Acute Myeloid Leukemia Claudia Haferlach and Torsten Haferlach 8. Targeting p53 Tumor Suppressor for AML Therapy Kensuke Kojima and Lyubumir T. Vassilev 9. AML-Selective Apoptosis Induction by rationally designed Death Ligand Fusion Protein Edwin Brenner and Wijnand Helfrich Part II: Signaling 10. PIM Kinases in AML Varsha. Gandhi and L. Chen 11. Development of Midostaurin as a Tyrosine Kinase Inhabitor Richard M. Stone and Gabi Motyckova 12. FLT3 in AML Naval Daver Farhad Ravandi 13. FLT3-ITD. Clinical (Sorafenib/AC220) Naveen Pemmeraju and Jorge E. Cortes 14. Nucleophosmin (NPM1) Kapil N. Bhalla and Ramesh Balusu 15. Raf/MEK Pathway James A. McCubrey, Linda.S. Steelman, Joerg Baesecke, and AlbertoM. Martelli 16. The Role of Translational Medicine in Optimization of Therapies targeting the RAS-MAP Kinase Pathway Judith S. Sebolt-Leopold 17. Clinical Use of Farnesyltransferase Inhititors Chezi Ganzel and Jacob M. Rowe 18. The P13K-AKT-mTOR signaling Network in AML Brandon Beagle and David A. Fruman 19. Targeting the P13 Kinase-mTOR Signaling Pathway in AML Martin Carroll 20. Aurora kinases Subrata Sen, Hiroshi Katayama 21. The Clinical Development of Aurora Kinase Inhibitors in Acute Myeloid Leukemia Kevin R. Kelly, Ciara L. Freeman, and Francis J. Giles Part III: Epigenetics 22. AML-Deacetylases Margherita Ghisi and Ricky W. Johnstone 23. Methylation in AML-Clinical Applications Naveen Pemmaraju, Guillermo Garcia-Manero, Farhad Ravandi Part IV: Nuclear Receptors 24. Topic: RARa/RXR Part: Basic Hugues de The 25. Arsenic Trioxide in Untreated APL Elihu H. Estey 26. Targeting PML-RARa with Retinoids Eytan M. Stein and Martin S. Tallman 27. NR4A Orphan Receptors as Drug Targets Steven H. Safe, Syng-Ook Lee, Cong Meng, and Beiyan Zhou Part V: Cell Surface Receptors 28. Antibody-based Therapeutics Targeting CD33, CD45, and CD66 Roland B. Walter, Oliver W. Press, and Irwin D. Bernstein Part VI: Stem Cells 29. New Heterogeneity of the Leukemic Stem Cells Dominique Bonnet 30. Targeting Leukemia Stem Cells Duane C. Hassane, Monica L. Guzman Part VII: Microenvironment 31. Regulation of Hematopoiesis by CXCL12/CXCR4 Signaling Daniel C. Link 32. CXC4/CXCL12 as a Therapeutic Target Geoffrey L. Uy, John F. DiPersio 33. VLA-4: A Cell’s Consequential Encounter Thalia Papayannopoulou 34. VLA-4 Function and Prognosis in Acute Myeloid Leukemia Pamela S. Becker, Frederick R. Appelbaum 35. VLA4 in Acute Lymphoblastic Leukemia Halvard Boenig, Yong-Mi Kim Part VIII: Hypoxia 36. The Leukemic Bone Marrow Microenvironment: Targeting Hypoxia with Hypoxia Activated Pro-Drugs Juliana Benito, Marina Konopleva, William R. Wilson Part IX: Micro-RNAs 37. Topic: miRs as Therapeutic Targets Maitri Shah, George Calin 38. Clinical Implications of MicroRNAs in AML Parvathi Ranganathan, Ramiro Garzon Part X: Metabolism 39. Inhibition of Glycolysis as a Therapeutic Strategy in Acute Myeloid Leukemias R. Laister, Tak W. Mak, Mark Minden 40. Molecular and Biochemical Basis for the Reprogramming of Intermediary Metabolism in Leukemia Cells Ismael Samudio, Juliana Velez Part XI: Cell Therapy 41. NK Cell Immunotherapy for AML Laurence James N. Cooper, Dean Anthony Lee, Elizabeth Shpall 42. Allogeneic and Autologous T cell Strategies to Enhance Targeting of Acute Myeloid Leukemia Gerrit Weber, Catherine M. Bollard, John Barrett 43. Indications for Hematopoietic Transplantation for AML Sairah Ahmed, Richard Champlin 44. Mesenchymal Stem/Stromal Cell Targeted Therapies for Solid Tumors and Hematological Malignancies Christopher H Booth, Lysette Mutkus, Karen Bussard, Erika Spaeth, Michael Andreeff, Frank C Marini
