The role of phosphorylation of MLF2 at serine 24 in BCR-ABL leukemogenesis

Abstract

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder defined by the presence of the fusion gene BCR-ABL1 in primitive hematopoietic progenitors. The myeloid leukemia factors (MLFs) were identified in the fly and human, and are involved in acute leukemia and enhancing the myeloid factor; however, the function of MLF2 in CML is poorly understood. In this study, we demonstrated that MLF2 may play an oncogenic role in CML. The expression level of MLF2 was related to the proliferation, colony-formation ability, and sensitivity to imatinib in K562 cells. Moreover, phosphorylation at serine 24, detected through Phos-tag sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was required to maintain the activity of MLF2 in CML. The effects of MLF2 overexpression on the colony-formation ability in vitro and mouse survival in vivo could be alleviated by point mutation of MLF2 at serine 24. These findings uncover the oncogenic role of MLF2 through phosphorylation at serine 24 and provide a novel therapeutic target in CML.