Linking CDK6 to Extracellular Vesicles

Acute myeloid leukemia (AML) is the most common acute leukemia in adults that still poses challenges for researchers, doctors, and patients alike. In a recent report by the American Cancer Society AML ranked 6th highest cancer-related death cause in the male population. The treatment modalities for AML include chemotherapy and hematopoietic stem cell transplantation, albeit the outcome is poor with a five year relative survival of only 17-19%. The leukemic cells are located in the bone marrow and cells within the bone marrow are able to communicate with each other by releasing extracellular vesicles. Extracellular vesicles include various factors which when taken up by surrounding cells can influence the cells behavior. Leukemic cells show an increased release of such vesicles which leads to an abnormal cell-cell communication and to the remodeling of the bone marrow niche during disease, which can support disease progression. There is a lack of tailored curative therapies for AML which might be overcome by considering vesicle regulation. In this project we will decipher how the cell cycle player CDK6 regulates those vesicles and if the inhibition of CDK6 in turn might affect the bone marrow niche cells. In addition, we shall investigate if CDK6 inhibition opens novel vulnerabilities for treatment options targeting vesicle regulators.