Identification of Genes Involved in Hematopoietic Stem Cell Differentiation and Leukemia Differentiation and Leukemia

摘要: Acute myeloid leukemia (AML) in adults has a 20% 5-year disease-free survival, despite treatment with aggressive cytotoxic chemotherapy. Heat shock protein (Hsp90) is chaperone for several client proteins involved transcriptional regulation, signal transduction and cell cycle control. 17-AAG, the synthetic analogue of geldanamycin (GA), an Hsp90 inhibitor that presently phase II clinical trials various other cancers. In Drosophila, functional inactivation resulted transdifferentiation event where eye tissue becomes limb-like outgrowth due to abnormal wingless expression (wg). Expression this phenotype induced by inhibition independent after being inherited across successive generations, suggesting epigenetic mechanism. Wnt signaling associated hematopoietic stem maintenance important progression. The objective study chapter 3 was determine whether pathway regulated mammalian cells through mechanisms as observed flies. Our preliminary data showed activation canonical precursor line, EML, Hsp90. This effect seemed be short lived pharmacological did not cause any changes activity during differentiation EML cells. However there considerable variability our results prevented further progress these studies. Further investigation into molecular mechanism adult needed play role maintaining leukemic state AML.