Project A6: The role of homeobox genes in erythroid leukemia
Acute erythroleukemia (AEL) is a rare subtype of AML. Although comprehensive genomic analysis confirmed genomic complexity of this subtype, the underlying biology of AEL is still not precisely defined. This is also due to the fact that there are only very few murine models recapitulating human AEL. In the previous funding periods, we could establish two mouse models which demonstrated a pivotal role of two members of the homeobox family of transcription factors in the development of this type of leukemia, the Para Hox gene Cdx4 and the non-clustered homeobox gene VENTX. It is known that clustered HOX genes play a major role in shaping stemness in the leukemic stem cell (LSC) compartment. In the following funding period, we want to investigate the phenotype, molecular, epigenetic and proteomic landscape of the LSC in AEL with respect to the involvement of clustered and non-clustered homeobox genes using the newly established VENTX and Cdx4 AEL models and the large clinically and molecular annotated biobank of the AMLSG. In addition, we aim at analyzing the functional impact of mutations identified in AEL patients for the development of AEL using CRISP/Cas technology and murine models.
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