Role for MKL1 in megakaryocytic maturation

被引：56

作者：

Cheng, Ee-chun

Luo, Qing ^{[2
]}

Bruscia, Emanuela M. ^{[3
]}

Renda, Matthew J.

Troy, James A.

Massaro, Stephanie A. ^{[3
]}

Tuck, David ^{[4
]}

Schulz, Vincent ^{[3
]}

Mane, Shrikant M. ^{[5
]}

Berliner, Nancy ^{[6
]}

Sun, Yi ^{[7
,8
]}

Morris, Stephan W. ^{[7
,8
]}

Qiu, Caihong ^{[9
]}

Krause, Diane S. ^{[1
,4
]}

机构：

[1] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA

[2] Chongqing Univ, Coll Bioengn, Project 111, Chongqing 630044, Peoples R China

[3] Yale Univ, Dept Pediat, New Haven, CT 06520 USA

[4] Yale Univ, Dept Pathol, New Haven, CT 06520 USA

[5] Yale Univ, WM Keck Facil, New Haven, CT 06520 USA

[6] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[7] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[8] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[9] Yale Univ, Yale Stem Cell Ctr, New Haven, CT 06520 USA

来源：

BLOOD | 2009年 / 113卷 / 12期

基金：

美国国家卫生研究院;

关键词：

SERUM RESPONSE FACTOR; ACUTE MEGAKARYOBLASTIC LEUKEMIA; WISKOTT-ALDRICH-SYNDROME; TRANSCRIPTIONAL COACTIVATOR; ACTIN DYNAMICS; GENE; INDUCTION; SRF; POLYPLOIDIZATION; T(1-22)(P13-Q13);

D O I：

10.1182/blood-2008-09-180596

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2009;113:2826-2834)

引用

页码：2826 / 2834

页数：9

共 52 条

[1] Cord blood in vitro expanded CD41+ cells:: identification of novel components of megakaryocytopoiesis [J].