Reduced Response to Stromal Cell-Derived Factor-1(SDF-1) May Lead to Low Expression of p57kip2 in the Bone Marrow of Patients with De Novo Myelodysplastic Syndromes (MDS)

To explore the expression of p57 in the bone marrow(BM) of patients with de novo myelodysplastic syndromes(MDS), and the role in MDS pathogenesis and prognosis, as well as the relationship between the expression of p57 and SDF-1/CXCR4 signal. Patients and Methods The expression of p57 and CXCR4 in bone marrow mononuclear cells (BMMCs) of 67 de novo MDS patients (including 46 low-risk, 21 high-risk according IPSS) were measured by real-time quantitative (RT)-PCR. BM CD34⁺ cell percentage was measured by flow cytometry. Besides, p57 expression was investigated when stromal cell-derived factor-1(SDF-1) was co-cultured with BMMCs from MDS cases and normal control respectively. Furthermore, comparison of p57 expression level before and after treatment in 25 MDS patients was studied. Results P57 expression was significantly decreased in MDS patients when compared to normal controls (p=0.003). Patients with abnormal karyotype showed lower expression of p57 compared to normal karyotype cases (P=0.028). A positive correlation between p57 and CXCR4 expression was investigated (r=0.609, P<0.001), and P57 expression was negatively correlated to BM CD34⁺ cell percentage (r=−0.393, P=0.008) in MDS patients. Additionally, P57 expression increased after treatment who received hematological response (P=0.016). P57 expression in BMMCs from normal control increased significantly when co-cultured with SDF-1 in vitro, which could be blocked by AMD3100, whereas SDF-1 induced a mild increase of p57 expression in MDS when compared to normal control (P<0.001). Conclusion Low expression of the p57 is common in MDS, which may play a role in pathogenesis and indicate poor prognosis. SDF-1 induced mild p57 expression increasing in MDS patients.

No relevant conflicts of interest to declare.