MKL1 promotes megakaryocytic differentiation in HEL cells

Megakaryoblastic Leukemia 1 (MKL1) was identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, but nothing is known regarding its role in hematopoiesis. Here we show that overexpression of MKL1 enhances megakaryocytic differentiation of the Human Erythroleukemia cell line (HEL). Microarray analysis reveals that MKL1 promotes expression of megakaryocyte-specific genes such as glycoprotein V (GP5), as well as cytoskeletal and adhesion molecule genes relevant to megakaryocyte differentiation and proplatelet formation. MKL1 is a transcriptional coactivator of Serum Response Factor. In this study, MKL1 also upregulates known SRF targets. Results provide insight into the role of MKL1 in megakaryocytopoiesis. Analysis of megakaryocytic human erythroleukemia (HEL) cells after 24 hours of TPA induced differentiation with MKL1 overexpression. Gene expression data for control/HEL cells and MKL1/HEL cells, which expresses high levels of MKL1 protein upon doxycycline addition, were determined. TPA, which was added to the samples to induce differentiation, was added together with doxycycline for 24 hours. The TPA differentiated MKL1/HEL samples with or without doxycyline induced MKL overexpression were done in duplicate and were used for both Affymetrix and Illumina platforms.