Main 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.

Contents:

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-RAR 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