Hypermethylation of SHP-1 promoter in patient with high-risk myelodysplastic syndrome and it predicts poor prognosis.
Summary of "Hypermethylation of SHP-1 promoter in patient with high-risk myelodysplastic syndrome and it predicts poor prognosis."
To study the role of SHP-1 methylation in the pathogenesis of myelodysplastic syndromes (MDS), we detect the methylation status of SHP-1 promoter and STAT3 phosphorylation of MDS patients by the methylation-specific PCR and Western blotting, respectively. It is found that the methylation rate of SHP-1 promoter of high-risk MDS patients (69.2%) was higher than that of the low-risk MDS patients (21.4%) (P = 0.001). The expression rate of STAT3 phosphorylated protein of high-risk group was higher (66.7%), when compared with that of the low-risk group (18.2%) (P = 0.0001). Correlation analysis showed that the methylation status of SHP-1 promoter is positive correlated with the expression of phosphorylated STAT3 in MDS patient (P < 0.001, r = 0.55). Interestingly, in high-risk group, the Kaplan-Meier analysis showed that the 3-year overall survival rate of high-risk MDS patients with SHP-1 methylation was lower than that of patient without SHP-1 methylation (25% vs. 61%) (P = 0.033). In summary, it is indicated that the SHP-1 methylation plays important role in the pathogenesis of MDS via activating the JAK/STAT pathway probably and the methylation of SHP-1 promoter is a useful prognostic factor for high-risk MDS patient, with the characteristic of higher methylation lower survival rate.
Affiliation
Department of Hematology, Tianjin Cancer Hospital and Institute, Tianjin Medical University, Tianjin, 300060, People's Republic of China, zhangzhurensci@yahoo.cn.
Journal Details
This article was published in the following journal.
Name: Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22258937
- DOI: http://dx.doi.org/10.1007/s12032-012-0163-6
Medical and Biotech [MESH] Definitions
Risk Reduction Behavior
Reduction of high-risk choices and adoption of low-risk quantity and frequency alternatives.
Hamartoma Syndrome, Multiple
A hereditary disease characterized by multiple ectodermal, mesodermal, and endodermal nevoid and neoplastic anomalies. Facial trichilemmomas and papillomatous papules of the oral mucosa are the most characteristic lesions. Individuals with this syndrome have a high risk of BREAST CANCER; THYROID CANCER; and ENDOMETRIAL CANCER. This syndrome is associated with mutations in the gene for PTEN PHOSPHATASE.
Brugada Syndrome
An autosomal dominant defect of cardiac conduction that is characterized by an abnormal ST-segment in leads V1-V3 on the ELECTROCARDIOGRAM resembling a right BUNDLE-BRANCH BLOCK; high risk of VENTRICULAR TACHYCARDIA; or VENTRICULAR FIBRILLATION; SYNCOPAL EPISODE; and possible sudden death. This syndrome is linked to mutations of gene encoding the cardiac SODIUM CHANNEL alpha subunit.
Myelodysplastic-myeloproliferative Diseases
Clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either MYELODYSPLASTIC SYNDROMES or MYELOPROLIFERATIVE DISORDERS.
Silver-russell Syndrome
Genetically and clinically heterogeneous disorder characterized by low birth weight, postnatal growth retardation, facial dysmorphism, bilateral body asymmetry, and clinodactyly of the fifth fingers. Alterations in GENETIC IMPRINTING are involved. Hypomethylation of IGF2/H19 locus near an imprinting center region of chromosome 11p15 plays a role in a subset of Silver-Russell syndrome. Hypermethylation of the same chromosomal region, on the other hand, can cause BECKWITH-WIEDEMANN SYNDROME. Maternal UNIPARENTAL DISOMY for chromosome 7 is known to play a role in its etiology.
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