Mechanism of A New DOT1L Inhibitor EPZ-5676 and Its Research Progress -Review / 中国实验血液学杂志

ABSTRACT

Leukemia carring translocation at the 11q23 locus is referred to MLL-rearranged (MLL-r) leukemia, and the occurrence of this genetic lesion is associated with a poor prognosis. The most common translocation chromosomes are chromosomes 4,9 and 10. Recently MLL protein was found to interact with DOT1L (DOT1-like) protein, which can promote leukemogenesis. A new DOT1L inhibitor EPZ-5676 can selectively inhibit proliferation, promote apoptosis and differentiation, which was also found to act synergistically with anti-AML (acute myeloid leukemia) and anti-ALL (acute lymphoblastic leukemia) drugs. EPZ-5676 can also induce sustained regression in a rat xenograft model of MLL-rearranged leukemia. Now the novel drug is in phase I of clinical trail. The results suggest that the EPZ-5676 is promising. In this article, the mechanism of EPZ-5676 and its research progress are reviwed.