Project A6: VENTX and its role in acute erythroid leukemia
In the last funding period, VENTX could be identified as a novel leukemogenic factor, which is able to induce acute erythroid leukemia (AEL) in the murine bone marrow transplantation model. Co-expression of VENTX with one of the most frequent fusion genes in AML, AML1-ETO, did not change the phenotype of leukemias generated, indicating that VENTX is a dominating factor in inducing acute leukemia with an erythroid phenotype. In line with these observations, expression analyses confirmed high expression of VENTX in primary human AEL. Taken together, these data assign an unsuspected and novel role to VENTX in the biology of AEL. There are very few models of AEL in mice, the best characterized strictly depending on the viral infection of mice with the Friend virus, described over 50 years ago. Thus, this model will be a valuable tool to improve our understanding of the biology of this AML subtype. The work program will aim at identifying the cell of origin in the established murine AEL model as well as in primary AEL patient samples. It will analyse, whether secondary genetic alterations, recurrently found in patients with AEL such as the NPM1 mutation, cooperate with VENTX in inducing AEL. Finally, the project will aim at dissecting the regulatory network of VENTX-induced erythroleukemia.
For a list of project-related publications, please go to this page