By Judith E. Karp
This is a well timed compilation of recent options within the molecular pathogenesis and molecular remedy of acute myelogenous leukemia (AML). the focal point is on chosen severe molecular determinants of AML pathogenesis and pathophysiology and the exploitation of those elements through various healing brokers and modalities. there's an emphasis all through at the bidirectional circulate of information among the medical and laboratory arenas.
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J Med Chern 1993;36:3496-3502. 63. Shyam K, Penketh PG, Loomis RH, Rose WC, Sartorelli AC. Antitumor 2-(aminocarbonyl)-1,2-bis (methylsulfony1)-I-(2-chloroethyl)-hydrazines. J Med Chern 1996;39:796-80 I. 64. Pratviel G, Shyam K, Sartorelli AC. Cytotoxic and DNA-damaging effects of 1,2-bis(sulfonyl)hydrazines on human cells of the Mer+ and Mer-phenotype. Cancer Biochem Biophys 1989; 10:365-375. 18 Part I I Ravandi and Giles 65. Penketh PG, Shyam K, Sartorelli AC. Comparison of DNA lesions produced by tumor-inhibitory 1,2-bis (sulfonyl)hydrazines and chloroethylnitrosoureas.
Finally, CBF activates the NF-l gene encoding the RAS-GAP neurofibromin, suggesting that repression of NF-l by CBF oncoproteins sensitizes leukemic cells to granulocute-macrophage colony-stimulating factor (GM-CSF) and perhaps other cytokines, as in juvenile myelomonocytic leukemia (JMML) cases associated with NF-l mutation (39). Inhibition of early differentiation in leukemic stem cells and reduction of apoptosis under stress conditions are expected to contribute to transformation by CBF oncoproteins, whereas G I-to-S blockade seems paradoxical and suggests a requirement for additional mutations that bypass cell cycle inhibition (Fig.
Li B, Dou QP. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci USA 2000;97:3850-3855. 155. Marshansky V, Wang X, Bertrand R, et al. Proteasomes modulate balance among proapoptotic and antiapoptotic Bcl-2 family members and compromise functioning of the electron transport chain in leukemic cells. J ImmunoI2001;166:3130-3142. 156. Gardner RC, Assinder SJ, Christie G, et al. Characterization of peptidyl boronic acid inhibitors of mammalian 20 Sand 26 S proteasomes and their inhibition of proteasomes in cultured cells.
Acute Myelogenous Leukemia (Contemporary Hematology) by Judith E. Karp