Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia

被引：0

作者：

A Sanchez-Aguilera

I Rattmann

D Z Drew

L U W Müller

V Summey

D M Lucas

J C Byrd

C M Croce

Y Gu

J A Cancelas

P Johnston

T Moritz

D A Williams

机构：

[1] Cincinnati Children's Hospital Medical Center,Division of Experimental Hematology

[2] Children's Hospital Boston,Division of Hematology/Oncology

[3] Ohio State University,Division of Hematology & Oncology

[4] Immunology and Medical Genetics,Department of Molecular Virology

[5] Ohio State University,Department of Internal Medicine (Cancer Research)

[6] Clinical Research Program,undefined

[7] Children's Hospital Boston,undefined

[8] West German Cancer Center,undefined

[9] University of Duisburg-Essen Medical School,undefined

来源：

Leukemia | 2010年 / 24卷

关键词：

RhoH GTPase; chronic lymphocytic leukemia; TCL1; B cells; lymphopoiesis;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family that functions as a regulator of thymocyte development and T-cell receptor signaling by facilitating localization of zeta-chain-associated protein kinase 70 (ZAP70) to the immunological synapse. Here we investigated the function of RhoH in the B-cell lineage. B-cell receptor (BCR) signaling was intact in Rhoh−/− mice. Because RhoH interacts with ZAP70, which is a prognostic factor in B-cell chronic lymphocytic leukemia (CLL), we analyzed the mRNA levels of RhoH in primary human CLL cells and showed a 2.3-fold higher RhoH expression compared with normal B cells. RhoH expression in CLL positively correlated with the protein levels of ZAP70. Deletion of Rhoh in a murine model of CLL (Eμ-TCL1Tg mice) significantly delayed the accumulation of CD5+IgM+ leukemic cells in peripheral blood and the leukemic burden in the peritoneal cavity, bone marrow and spleen of Rhoh−/− mice compared with their Rhoh+/+ counterparts. Phosphorylation of AKT and ERK in response to BCR stimulation was notably decreased in Eμ-TCL1Tg;Rhoh−/− splenocytes. These data suggest that RhoH has a function in the progression of CLL in a murine model and show RhoH expression is altered in human primary CLL samples.

引用

页码：97 / 104

页数：7

共 153 条

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