Involvement of RhoH GTPase in the Development of B-Cell Chronic Lymphocytic Leukemia

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.

• Publication year

  2009

• Venue

  Leukemia

• Publication date

  2009-10-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/leu.2009.217PMID 19847197PMCID 3869226
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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