Expression of proteins regulating apoptosis (BCL-2, MCL-1, BCL-X and BAX) in acute myeloid leukemia (AML) blasts at diagnosis have been shown to be associated with disease-free survival. The concentrations of these proteins are combined in the Anti Apoptotic index (AAI). We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. This suggested a dynamic regulation of apoptosis. We hypothesized that expression of apoptosis-related proteins in AML blasts, and possibly also in bystander cells in the bone marrow, is regulated by extracellular factors present in the AML microenvironment. Tumor cell communication with its microenvironment is emerging as an important determinant playing multiple roles in cancer. Both soluble factors and extracellular vesicles (EVs), most notably exosomes, have been shown to influence cellular processes of malignant and normal cells in the tumor microenvironment. We performed a proteomics analysis of the whole secretome as well as of EVs secreted by AML blasts to pinpoint released protein factors that might mediate apoptosis-resistance.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Human ; AML ; secretome ; exosome ; extracellular vesicles ; acute myloid leukemia ; Anti Apoptotic Index
Principal Investigators: (in alphabetical order) |
Dr Connie Ramona Jimenez |
Submitting User: | ccms |
Wojtuszkiewicz A, Schuurhuis GJ, Kessler FL, Piersma SR, Knol JC, Pham TV, Jansen G, Musters RJ, van Meerloo J, Assaraf YG, Kaspers GJ, Zweegman S, Cloos J, Jimenez CR.
Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis.
Mol. Cell Proteomics. 2016 Apr;15(4):1281-98. Epub 2016 Jan 22.
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