Vol 49, No 1 (2011)
Original paper
Published online: 2011-04-19
ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population
DOI: 10.5603/FHC.2011.0008
Folia Histochem Cytobiol 2011;49(1):49-54.
Abstract
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 anti-tumor 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 upregulation 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 upregulate the production of interleukin-2, but
superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role 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 the
Polish population. 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 ICOS ISV1+173T>C (rs10932029),
ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried
out using allelic discrimination methods with the TaqMan® SNP Genotyping Assay. There were no statistically
significant differences in the allele, genotype, or 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 ICOS 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 to other individuals. This indicates 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. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 49–54)
Keywords: ICOSpolymorphismsB-CLL
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