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Underexpression of RhoH in Hairy Cell Leukemia

¹ Institut National de la Santé et de la Recherche Medicale U.837, Centre Jean-Pierre Aubert, Institut de Recherches sur le Cancer de Lille and Université Droit et Santé de Lille II, Lille, France; ² Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Caen, Caen, France; ³ Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and ⁴ Gundersen Lutheran Medical Foundation, La Crosse, Wisconsin

Requests for reprints: Carl Simon Shelley, Gundersen Lutheran Medical Foundation, La Crosse Medical Health Science Center, 1300 Badger Street, La Crosse, WI 54601. Phone: 608-789-8952; Fax: 608-775-6602; E-mail: carlsimonshelley{at}yahoo.com.

Key Words: leukemia • adhesion • migration

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. [Cancer Res 2008;68(12):4531–40]