Role for MKL1 in megakaryocytic maturation.

Abstract:

:Megakaryoblastic leukemia 1 (MKL1), identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, is highly expressed in differentiated muscle cells and promotes muscle differentiation by activating serum response factor (SRF). Here we show that Mkl1 expression is up-regulated during murine megakaryocytic differentiation and that enforced overexpression of MKL1 enhances megakaryocytic differentiation. When the human erythroleukemia (HEL) cell line is induced to differentiate with 12-O-tetradecanoylphorbol 13-acetate, overexpression of MKL1 results in an increased number of megakaryocytes with a concurrent increase in ploidy. MKL1 overexpression also promotes megakaryocytic differentiation of primary human CD34(+) cells cultured in the presence of thrombopoietin. The effect of MKL1 is abrogated when SRF is knocked down, suggesting that MKL1 acts through SRF. Consistent with these findings in human cells, knockout of Mkl1 in mice leads to reduced platelet counts in peripheral blood, and reduced ploidy in bone marrow megakaryocytes. In conclusion, MKL1 promotes physiologic maturation of human and murine megakaryocytes.

journal_name

Blood

journal_title

Blood

authors

Cheng EC,Luo Q,Bruscia EM,Renda MJ,Troy JA,Massaro SA,Tuck D,Schulz V,Mane SM,Berliner N,Sun Y,Morris SW,Qiu C,Krause DS

doi

10.1182/blood-2008-09-180596

subject

Has Abstract

pub_date

2009-03-19 00:00:00

pages

2826-34

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2008-09-180596

journal_volume

113

pub_type

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