Underexpression of RhoH in Hairy Cell Leukemia.
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.
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.
Sylvie
S
Galiègue-Zouitina
Laure
L
Delestré
Caroline
C
Dupont
Xavier
X
Troussard
Carl Simon
CS
Shelley
D000818:Animals; D015153:Blotting, Western; D039521:CD11c Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002908:Chronic Disease; D005434:Flow Cytometry; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013160:Splenic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D039521:CD11c Antigen; C447841:RhoH protein, human; C496930:RhoH protein, mouse; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins