TY - JOUR
T1 - Prognostic implication and biological roles of RhoH in acute myeloid leukaemia
AU - Iwasaki, Toshihiro
AU - Katsumi, Akira
AU - Kiyoi, Hitoshi
AU - Tanizaki, Ryohei
AU - Ishikawa, Yuichi
AU - Ozeki, Kazutaka
AU - Kobayashi, Miki
AU - Abe, Akihiro
AU - Matsushita, Tadashi
AU - Watanabe, Takashi
AU - Amano, Mutsuki
AU - Kojima, Tetsuhito
AU - Kaibuchi, Kozo
AU - Naoe, Tomoki
PY - 2008/12
Y1 - 2008/12
N2 - The Rho family of small GTPases, including Rho, Rac and Cdc42, has been well characterised as a molecular switch that transduces signals from plasma membrane to the downstream effectors. RhoH gene, a member of the Rho family, is specifically expressed in haematopoietic cells. The known function of RhoH is antagonising Rac and mediating activation of ZAP-70 in T lymphocytes; however, biological roles of RhoH in myeloid cells remain unknown. Here, we analysed the prognostic implication of the expression level of the RhoH gene transcript in bone marrow samples from 90 newly diagnosed acute myeloid leukaemia (AML) patients using a real-time fluorescence detection method. Kaplan-Meier analysis demonstrated that low expression of the RhoH transcript was a predictor of worse prognosis in both overall and disease-free survival. Multivariate analysis demonstrated that low expression of RhoH was an independent unfavourable prognostic factor for both overall and disease-free survival of AML patients. Overexpression of RhoH leads to dephosphorylation of Bad at Serine 75 residue possibly through deactivation of Rac. It is possible that low expression of RhoH (i.e. high GTP-Rac) contributes to chemotherapy resistance in leukaemia cells. Our result suggests that inhibition of Rac and its signalling components might provide a useful anti-leukaemic strategy.
AB - The Rho family of small GTPases, including Rho, Rac and Cdc42, has been well characterised as a molecular switch that transduces signals from plasma membrane to the downstream effectors. RhoH gene, a member of the Rho family, is specifically expressed in haematopoietic cells. The known function of RhoH is antagonising Rac and mediating activation of ZAP-70 in T lymphocytes; however, biological roles of RhoH in myeloid cells remain unknown. Here, we analysed the prognostic implication of the expression level of the RhoH gene transcript in bone marrow samples from 90 newly diagnosed acute myeloid leukaemia (AML) patients using a real-time fluorescence detection method. Kaplan-Meier analysis demonstrated that low expression of the RhoH transcript was a predictor of worse prognosis in both overall and disease-free survival. Multivariate analysis demonstrated that low expression of RhoH was an independent unfavourable prognostic factor for both overall and disease-free survival of AML patients. Overexpression of RhoH leads to dephosphorylation of Bad at Serine 75 residue possibly through deactivation of Rac. It is possible that low expression of RhoH (i.e. high GTP-Rac) contributes to chemotherapy resistance in leukaemia cells. Our result suggests that inhibition of Rac and its signalling components might provide a useful anti-leukaemic strategy.
UR - http://www.scopus.com/inward/record.url?scp=56649092609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56649092609&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0609.2008.01132.x
DO - 10.1111/j.1600-0609.2008.01132.x
M3 - Article
C2 - 18691253
AN - SCOPUS:56649092609
SN - 0902-4441
VL - 81
SP - 454
EP - 460
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 6
ER -