The PTPN22 R620W Polymorphism Is Not Associated With Clinical and Molecular Correlates Of Chronic Lymphocytic Leukemia (CLL) In Patients Originating From a Region With Low Prevalence Of The Autoimmunity Risk Variant

PTPN22 is a protein tyrosine phosphatase that modulates antigen-receptor signaling in T and B cells. A PTPN22 R620W polymorphic allele (C1858T, rs2476601) has been associated with increased risk for the development of multiple autoimmune diseases in patients originating from Northwestern Europe, whereas this association is less clear in patients originating from Southern Europe where the 620W (1858T) allele is less frequent. A higher frequency of the 620W risk allele has recently been reported in Chronic lymphocytic leukemia (CLL) patients originating from Northwest Europe. These data adds to the recent findings that PTPN22 is markedly overexpressed in the majority of CLL patients and possibly contributes to the pathogenesis of the disease by affecting apoptosis/survival of antigen stimulated CLL B-lymphocytes.

In order to extend further those observations we conducted a retrospective study on the frequency of the PTPN22 R620W variant in 87 CLL patients and 108 age/sex matched normal controls without a history of malignant disease originating from the Republic of Macedonia (Southeastern Europe) and compared the association of the variant with various clinical/molecular correlates.

Similar allele frequency of the minor T allele (0.06 and 0.063) and genotype distribution (0.88, 0.115 and 0.005 of CC, CT and TT genotypes) was found in CLL patients and normal controls, respectively. Both study groups were in Hardy-Weinberg equilibrium. Also, the PTPN22 R620W variant was not associated with any of the studied clinical and biological parameters, such as blood counts, CD38 expression, IGHV mutation status, incidence of autoimmune hemolytic anemia and autoimmune thrombocytopenia, immunoglobulin levels, time-to-treatment, progression free survival and overall survival.

We conclude that the PTPN22 R620W variant is not a risk factor for the development or progression of CLL in patients originating from the Southeastern European region. The differences of our data from the reported findings for CLL patients originating from Northwest Europe mirrors the differences observed in patients with various autoimmune diseases, suggesting a possible gene-environmental factor that affects the influence of the R620W variant on lymphocyte homeostasis.