The CXCL12-3′A allele plays a favourable role in patients with multiple myeloma

Abstract

Multiple myeloma (MM) is a plasma cell malignancy characterized by bone marrow infiltration and the presence of a monoclonal protein in serum and/or urine. CXCR4 and its ligand CXCL12 are essential for neoplastic cell homing to bone marrow in haematological malignancies. The JAK2/STAT3 pathway, which is activated after CXCL12 binding to CXCR4, takes part in many signalling cascades which are linked to cell proliferation and cell survival. Constitutive activation of this pathway plays an important role in tumourigenesis and malignant transformation. The present study aimed to determine the association between the polymorphic features located within the CXCR4 (rs2228014) and CXCL12 (rs1801157) encoding genes and disease susceptibility and progression.For this purpose 172 individuals including 54 patients with MM and 118 healthy controls were typed for the CXCL12 (A/G) and CXCR4 (C/T) alleles using the PCR-RFLP technique.The CXCL12 alleles and genotypes segregated similarly among patients and controls while the CXCR4 T variant was less frequently represented among patients (OR=0.074, p<0.001). All patients with the CXCR4 T allele and 16 out of 48 with wild type genotype presented with grade III of MM according to the International Staging System (ISS) (p=0.047).The CXCL12-3′A variant was more frequently detected in patients with less advanced MM (9/17 vs. 7/38, p=0.012 for patients in stage IA or IIA vs. IIB, IIIA and IIIB, respectively). Moreover, patients lacking the CXCL12-3′A variant more frequently presented with ISS II-III (32/38 vs. 5/13, p=0.003 for patients lacking CXCL12-3′A with ISS>I vs. ISS=I).This favourable effect of the CXCL12-3′A allele was also seen in the analysis of patient survival (p<0.05). The impact of the CXCL12-3′A allele was confirmed by multivariate analyses.In conclusion, these results imply that the CXCL12-3′A allele plays a favourable role in patients with multiple myeloma.