SDF-1/CXCR4 signal is involved in decreased expression of p57kip2 in de novo MDS patients

Abstract

P57kip2 is considered as a candidate tumor suppressor gene involvement in cell cycle control. In this study, we explored the expression of p57kip2 in various myelodysplastic syndrome (MDS) subsets by real-time quantitative PCR, as well as the relationship between p57kip2 and CXC receptor 4 (CXCR4). We also searched the role of stromal cell-derived factor-1 (SDF-1)/CXCR4 signal in p57kip2 expression in vitro. The expression of p57kip2 decreased in MDS cases (low grade MDS, P<0··001, n = 46; high grade MDS, P<0··001, n = 21), compared with that in control group. Patients with poor karyotype (according to IPSS) had lower p57kip2 than that in the normal group (P<0··05). P57kip2 expression increased after treatment with decitabine in the cases that had achieved response (P = 0··009, n = 7). Additionally, a positive correlation between p57kip2 and CXCR4 was investigated (r = 0··652, P<0··001, n = 67). P57kip2 expression in bone marrow mononuclear cells of normal controls increased significantly when co-cultured with SDF-1 in vitro, which could be blocked by AMD3100, whereas SDF-1 only induced a mild increase in p57kip2 in MDS. In conclusion, low expression of p57kip2 is common in MDS, which may play an important role in MDS pathogenesis. Reduced response to SDF-1 contributed to low expression of p57kip2 in MDS cases.

Keywords:

• p57kip2
• MDS
• SDF-1/CXCR4
• pathogenesis

Acknowledgements

This study was supported in part by the National Nature science foundation of China (Grant No. NNSFC81170463).