Proteomics

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Human AML secretome and exosomes and correlation with Anti-Apoptotic Index, part 4


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bone Marrow, Bone Marrow Cell

DISEASE(S): Acute Leukemia

SUBMITTER: Sander Piersma  

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD003478 | Pride | 2016-02-03

REPOSITORIES: Pride

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Publications

Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis.

Wojtuszkiewicz Anna A   Schuurhuis Gerrit J GJ   Kessler Floortje L FL   Piersma Sander R SR   Knol Jaco C JC   Pham Thang V TV   Jansen Gerrit G   Musters René J P RJ   van Meerloo Johan J   Assaraf Yehuda G YG   Kaspers Gertjan J L GJ   Zweegman Sonja S   Cloos Jacqueline J   Jimenez Connie R CR  

Molecular & cellular proteomics : MCP 20160122 4


Expression of apoptosis-regulating proteins (B-cell CLL/lymphoma 2 - BCL-2, Myeloid Cell Leukemia 1 - MCL-1, BCL-2 like 1 - BCL-X and BCL-2-associated X protein - BAX) in acute myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showe  ...[more]

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