[Experimental study of SHP-1 promoter methylation in myelodysplastic syndromes and its related mechanism].
OBJECTIVE
To explore the role of SHP-1 promoter methylation on the pathogenesis and progression in myelodysplastic syndromes (MDS) and its related mechanism.


METHODS
63 MDS patients were divided into low-grade (LG) group and high-grade (HG) group according to IPSS score system. Bone marrow samples were collected. Methylation specific-PCR (MSP) were used to detect the status of SHP-1 promoter methylation in bone marrow (BM) samples from different risk MDS patients and MDS cell line, SKK-1. Western blot was used to detect signal transduction and activator of transcription (STAT3) activation in SKK-1 cell line and MDS patients.


RESULTS
No SHP-1 promoter methylation could be detected in healthy controls BM. Partially methylation was found in SKK-1 cell line. Methylation rate of SHP-1 gene promoter was found in BM of 24.2% of low-grade MDS patients and 63.3% of high-grade MDS patients, the difference between these two groups was statistically significant (P < 0.05); Patients were divided into different groups according to WHO subtype, chromosomal karyotype and blast cells in bone marrow, methylation rates of SHP-1 were significantly higher in RAEB-II, poor karyotype group and samples with 0.11-0.19 blast cells (P < 0.05); The phosphorylation protein of STAT3 was detected in SKK-1 cell line. The expression of phosphorylation STAT3 was significantly higher in HG group than in LG group (66.7% vs 18.2%) (P < 0.05). There was a significant correlation between SHP-1 promoter methylation and STAT3 phosphorylation.


CONCLUSIONS
Abnormal methylation of SHP-1 gene promoter might have tentative role in the pathogenesis and progression of MDS, which may be involved in STAT3 activation. Detection of SHP-1 promoter methylation may be helpful to evaluate the prognosis of MDS.
Department of Hematology, General Hospital of People's Liberation Army, Beijing 100853, China.
Yi-Zhuo
YZ
Zhang
Dan-Dan
DD
Zhao
Wei-Peng
WP
Zhao
Hai-Feng
HF
Zhao
Zhi-Gang
ZG
Zhao
Ya-Fei
YF
Wang
Xiao-Xiong
XX
Wu
Xiao-Ping
XP
Han
Wan-Ming
WM
Da
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055815:Young Adult
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6