Folia Histochemica et Cytobiologica (Apr 2011)

ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

  • Lidia Karabon,
  • Anna Jedynak,
  • Anna Tomkiewicz,
  • Dariusz Wolowiec,
  • Marek Kielbinski,
  • Dariusz Woszczyk,
  • Kazimierz Kuliczkowski,
  • Irena Frydecka

Journal volume & issue
Vol. 49, no. 1
pp. 49 – 54

Abstract

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There is strong evidence that altered immunological function entails an increased risk of B-cell chroniclymphocytic 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-cellsurface 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 forantibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normalantibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, butsuperinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibilitylocus to B-CLL. Therefore an extended study was undertaken to evaluate the association between fourICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in thePolish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on fourpolymorphisms 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 carriedout using allelic discrimination methods with the TaqMan® SNP Genotyping Assay. There were no statisticallysignificant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthycontrols for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patientscarrying 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 modulatethe risk of B-CLL in the Polish population, but are associated with disease dynamics, in particular with the timeto Rai stage progression.

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