Investigating the long-term and genome-wide effects of the AF4-MLL fusion protein

The oncoprotein AF4-MLL has been shown to induce proB ALL in a murine model system, by using retroviral gene transfer into murine LSK cells and subsequent transplanation experiments into lethally irradiated mice. Leukemia development took about 6.5 month (Bursen et al., 2010). We also affinity-purified the AF4-MLL fusion protein complex and demonstrated its aberrant functions in vitro (hyperactive P-TEFb kinase, increased H3K4me3 and H3K79me3 signatures; Benedikt et al., 2011). Here, we will summarize our efforts to model AF4-MLL-mediated functions of in an in vitro model system, in order to trace the specific effects exerted by AF4-MLL in a genome wide manner. We will summarize the status quo of our efforts and our ongoing work.

This work is supported by the grant Ma 1876/10 – 1 from the DFG.