Underexpression of RhoH in Hairy Cell Leukemia

Cancer Res. 2008 Jun 15;68(12):4531-40. doi: 10.1158/0008-5472.CAN-07-5661.

Abstract

The cause of hairy cell leukemia (HCL) is unknown. Current treatments seem effective only for a limited period of time. In addition, a significant proportion of patients remain refractive to all treatment options. These considerations indicate the need to develop alternative therapeutic strategies for HCL. Here, we report that HCL is characterized by underexpression of RhoH. In vitro reconstitution of RhoH expression inhibits the aberrant adhesion and transendothelial migration that drives disease pathogenesis. In an in vivo model of HCL, RhoH reconstitution limits malignant progression and protects against mortality. These findings provide the proof of principle that RhoH reconstitution represents a potential new approach to the treatment of HCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CD11c Antigen / metabolism
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Cell Proliferation
  • Chronic Disease
  • Flow Cytometry
  • Humans
  • Leukemia, Hairy Cell / genetics
  • Leukemia, Hairy Cell / metabolism*
  • Leukemia, Hairy Cell / pathology
  • Leukocytes
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Lymphoma / genetics
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Male
  • Mice
  • Mice, SCID
  • Promoter Regions, Genetic
  • Spleen / metabolism
  • Spleen / pathology
  • Splenic Neoplasms / genetics
  • Splenic Neoplasms / metabolism*
  • Splenic Neoplasms / pathology
  • Thrombocythemia, Essential / genetics
  • Thrombocythemia, Essential / metabolism*
  • Thrombocythemia, Essential / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • CD11c Antigen
  • RhoH protein, human
  • RhoH protein, mouse
  • Transcription Factors
  • rho GTP-Binding Proteins