Significance of Methylation State in SHP-1 Gene in B-cell Lymphoma

[Objective] To investigate the methylation state of CpG island in the SHP-1 gene promoter which is one of the negative regulators of JAK/STAT signaling pathway and to evaluate its significance in B-cell lymphoma. [Methods] Sixty-one paraffin specimens including 52 specimens of B-cell non-Hodgkin lymphoma and 9 specimens of benign lymphnodes proliferation and 15 specimens of blood mononuclear cells from health individuals were studied, methylation state of CpG island in SHP-1 gene in the specimens and Raji cell line were detected by methylation specific PCR(MSP) and unmethylation-specific PCR(un-MSP). The expression level of SHP-1 in Raji cells with or without 5-aza-2'-deoxyoytidine treatment were detected by reverse transcriptase PCR(RT-PCR).The inhibitory ratio of Raji cells were measured by MTT assay. [Results] The frequency of methylation in SHP-1 gene promoter in large B-cell lymphoma(DLBCL) and follicular lymphoma(FL) were 94% and 97%,respectively.In control group, however,9 specimens of benign lymphnodes proliferation and 15 specimens of blood mononuclear cells from health individuals showed no methylation in CpG island of SHP-1 gene promotor(P 0.0001). The expression of SHP-1 was recovered and the cell growth was inhibited when the cell exposed to the demethylating reagent. [Conclusion] SHP-1 gene silencling with aberrant CpG methylation is probably one of the critical events to the onset of B-cell lymphoma as well as important implications for the diagnostic markers and the target of gene therapy.