ICOS Gene Polymorphisms In B-Cell Chronic Lymphocytic Leukemia In a Polish Population

Abstract 4614 Introduction: There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an antitumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated a role of ICOS gene as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in a Polish population. Methods: A case-control study of 296 individuals including 146 B-CLL patients was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOSISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was done using allelic discrimination methods with the TaqManÒ SNP Genotyping Assay. Results: There were no statistically significant differences in the allele, genotype, and haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patients carrying genotype ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C [GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35 vs. 40.8%, p=0.013) compared with other individuals. Conclusion: This study showed that the investigated polymorphisms do not modulate the risk of B-CLL in the Polish population, but are associated with disease dynamics in particular with the time to Rai stage progression. Disclosures: No relevant conflicts of interest to declare.