SDF-1/CXCR4 signal is involved in decreased expression of p57kip2 in de novo MDS patients.
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.
Department of Hematology, Shanghai Sixth People’s Hospital affiliated to Shanghai Jiao Tong University, China.
Youshan
Y
Zhao
Juan
J
Guo
Shucheng
S
Gu
Xi
X
Zhang
Xiao
X
Li
Chunkang
C
Chang
D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12 / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
D054377:Chemokine CXCL12; D050761:Cyclin-Dependent Kinase Inhibitor p57; D019718:Receptors, CXCR4