Detection of CBFbeta/MYH11 fusion transcripts and study of the mechanism of leukemogenesis of CBFbeta/SMHHC fusion protein.
- Author:
Shi-cai XU
1
;
Lin YANG
;
Xu ZHOU
;
Min FENG
;
Yu-shu HAO
;
Zhi-jian XIAO
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Female; Humans; Leukemia, Myelomonocytic, Acute; genetics; metabolism; Male; Oncogene Proteins, Fusion; genetics; metabolism; Transcription, Genetic
- From: Chinese Journal of Hematology 2005;26(6):332-335
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore CBFbeta/MYH11 fusion transcripts and its expressing product CBFbeta/SMHHC fusion protein in mechanism of leukemogenesis.
METHODSCBFbeta/MYH11 fusion transcripts were detected by combined RT-PCR with sequencing. Transcription assays were examined using pM-CSFR-Luc as reporting plasmid, and subcellular localization of encoding proteins were assayed by double immunofluorescent staining and Western blot.
RESULTSTwo types of CBFbeta/MYH11 fusion transcripts were found in 26 patients with acute leukemia, most being of type A (23/26 cases, 92%) and a few of type D (2/26 cases, 8%). The inhibition of CBF-mediated M-CSFR promotor transactivation by CBFbeta/SMHHC fusion protein was increasing with the increase in amount of the fusion protein. CBFalpha subunit (AML1) located in nucleus, both CBFbeta subunit (CBFbeta) and CBFbeta/SMHHC located in cytoplasm. When AML1 and CBFbeta were coexpressed, CBFbeta still located mainly in cytoplasm, but when AML1 and CBFbeta/SMHHC were coexpressed, CBFbeta/SMHHC located mainly in nucleus.
CONCLUSIONS(1) The types of CBFbeta/MYH11 fusion transcripts of Chinese leukemia patients are almost the same as that reported in western literature. (2) CBFbeta/SMHHC inhibits CBF-mediated transactivation through competing with CBFbeta for binding to AML1.
