Determining the Mechanism of Anti-Leukemic Drug Ro5-3335 Using an Inducible Leukemic Mouse Model

Authors

• EE Rapp
• JL Diemer
• PP Liu

Abstract

In humans, an inversion of chromosome 16 resulting in the fusion of CBFB and MHY11 genes has been associated with the M4Eo subtype of Acute Myeloid Leukemia (AML). CBFß, in complex with the transcription factor RUNX1, is necessary for normal hematopoiesis. The aberrant fusion protein CBFß-MYH11 results in the cytoplasmic sequestration of RUNX1 and inhibition of its transcriptional regulator function. Using a Cre recombinase-inducible knock-in mouse model that recapitulates the CBFß-MYH11 fusion, we can study the development of inv(16) AML in mice with the hope of discovering new therapy options for patients. We previously identified anti-leukemic activity of a small molecule Ro5-3335, but the exact mechanism of action has yet to be clarified. We are using flow cytometry, cell cycle assays and colony forming assays to determine Ro5-3335’s effect on primary cells from non-leukemic, pre-leukemic, and leukemic mice. Our data suggest that Ro5-3335 has an anti-proliferative and pro-differentiation effect on the pre-leukemic and leukemic cells.

Scientific Focus Area: Genetics and Genomics

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