MLL-Rearranged ALL Cells Are Highly Dependent On the Expression of EP300-Interacting Inhibitor of Differentiation 1 (EID1)

Abstract 1462

MLL-rearranged acute lymphoblastic leukemia (ALL) remains a difficult to treat type of leukemia, for which alternative and more adequate treatment options are still urgently needed. Various genome-wide transcriptome studies, including ours, have shown that MLL-rearranged ALL patients display highly unique gene expression profiles. In search of new and valid therapeutic targets to which more adequate treatments could be developed, we constantly screen our gene expression profiling data for potential candidates. In the present study we set out to investigate EID1 (EP300-interacting inhibitor of differentiation 1), which we found highly and specifically expressed in MLL-rearranged ALL cells. Validating this observation, quantitative RT-PCR analysis confirmed that EID1 expression was significantly higher in MLL-rearranged ALL cells as compared with other ALL subtypes or healthy bone marrow samples. Next, we performed shRNA-mediated knockdown of EID1 in MLL-rearranged ALL cells, which resulted in a dramatic reduction of viable cells. Subsequently, flow cytometry analyses demonstrated that this rapid reduction of cell viability was due to massive induction of apoptosis as well as an abrupt cell cycle arrest. Consequently, it appeared difficult to study the actual function of EID1 over-expression in MLL-rearranged ALL cells. On the other hand, these features make EID1 an attractive target for therapeutic intervention in MLL-rearranged ALL. Hence, further studies on the function of EID1 in MLL-rearranged ALL and exploring the possibilities to inhibit it are warranted.