By Judith E. Karp
This is a well timed compilation of recent techniques within the molecular pathogenesis and molecular remedy of acute myelogenous leukemia (AML). the focal point is on chosen serious molecular determinants of AML pathogenesis and pathophysiology and the exploitation of those elements by way of varied healing brokers and modalities. there's an emphasis all through at the bidirectional circulate of data among the medical and laboratory arenas.
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Extra resources for Acute Myelogenous Leukemia (Contemporary Hematology)
Chapter 1 I AML Treatment: Biological Perspective 23 185. Kang CD, Yoo SD, Hwang BW, et al. The inhibition of ERKIMAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in chronic myelogenous leukemic K562 cells. Leuk Res 2000;24: 527-534. 186. Kim SC, Hahn JS, Min YH, Yoo NC, Ko YW, Lee Wl Constitutive activation of extracellular signal-regulated kinase in human acute leukemias: combined role of activation of MEK, hyperexpression of extracellular signal-regulated kinase, and downregulation of a phosphatase, PAC1.
Each approach will obviously need to be tailored to relevant AML subsets. For example, HDAC inhibitors are expected to target AMLl-ETO and PML-RARa but not MLL fusion oncoproteins, which transactivate HOX genes to induce cell proliferation. And small molecule or anti-sense inhibitors of CBF~ SMMHC will be useful only for the treatment of AMLs harboring this protein. I expression or activity may have broader application, but need to be evaluated for the possibility that these normal factors will stimulate cell cycle or inhibit apoptosis without inducing differentiation or cell cycle arrest because of the presence of additional genetic changes.
Issa IP, Garcia-Manero G, Giles Fl, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2' -deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; I03(5): 1635-1640. 43. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. 1 Clin Oncol 2002;20:2429-2440. 44. Kornblith AB, Herndon JE, II, Silverman LR, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study.
Acute Myelogenous Leukemia (Contemporary Hematology) by Judith E. Karp