[Detection of CBFbeta/MYH11 fusion transcripts and study of the mechanism of leukemogenesis of CBFbeta/SMHHC fusion protein].
OBJECTIVE
To explore CBFbeta/MYH11 fusion transcripts and its expressing product CBFbeta/SMHHC fusion protein in mechanism of leukemogenesis.


METHODS
CBFbeta/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.


RESULTS
Two 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.
Xu
Shi-cai
SC
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS & PUMC, Tianjin 300020, China.
Yang
Lin
L
Zhou
Xu
X
Feng
Min
M
Hao
Yu-shu
YS
Xiao
Zhi-jian
ZJ
D000328:Adult; D005260:Female; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D015514:Oncogene Proteins, Fusion