Prognostic implication and biological roles of RhoH in acute myeloid leukaemia.
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.
Iwasaki
Toshihiro
T
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Katsumi
Akira
A
Kiyoi
Hitoshi
H
Tanizaki
Ryohei
R
Ishikawa
Yuichi
Y
Ozeki
Kazutaka
K
Kobayashi
Miki
M
Abe
Akihiro
A
Matsushita
Tadashi
T
Watanabe
Takashi
T
Amano
Mutsuki
M
Kojima
Tetsuhito
T
Kaibuchi
Kozo
K
Naoe
Tomoki
T
D000328:Adult; D001853:Bone Marrow / Q000201:enzymology / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000201:enzymology / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis*
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C447841:RhoH protein, human; D014157:Transcription Factors; D051746:ZAP-70 Protein-Tyrosine Kinase; D051057:Proto-Oncogene Proteins c-akt; D020741:rho GTP-Binding Proteins