MEF2C and CEBPA: Possible co-regulators in chronic myeloid leukemia disease progression

Chronic myelogenous leukemia (CML), a hematopoietic malignancy, characterized initially by a chronic phase (CP) progresses into blast crisis (BC) with the accumulation of secondary abnormalities. We have reported earlier that MEF2C, a target of miR-223, was significantly up regulated in CML and also showed a negative correlation with miR-223. In this study, gene expression arrays were used to identify the genes regulated by MEF2C during myelopoiesis. Statistical tools were used to understand the correlation between MEF2C and the targets in different phases of CML. Different CML cell lines and CML patient samples were treated with imatinib to study the effect of MEF2C on the target genes. We observed that MEF2C targets a set of myeloid genes including the myeloid transcription factor CEBPA. MEF2C and CEBPA expression patterns are negatively correlated in CML patient samples. We further show that the expression of MEF2C and CEBPA along with CSF3R is sufficient to molecularly classify different stages of CML. Imatinib, the drug of choice for CML, abrogates MEF2C expression and reverses CEBPA repression both in the cell line and the primary cells. We report the existence of a MEF2C and CEBPA correlation in CML disease progression.