A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon alpha

Kreil, Sebastian, Waghorn, Katherine, Ernst, Thomas, Chase, Andrew, White, Helen, Hehlmann, Rudiger, Reiter, Andreas, Hochhaus, Aandreas and Cross, Nicholas C.P. , German CML Study Group (2010) A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon alpha. Haematologica, 95 (1), 148-152. (doi:10.3324/haematol.2009.011510).

Abstract

Interferon alpha (IFN) induces variable responses in chronic myeloid leukemia (CML), with 8-30% of early chronic phase cases achieving a complete cytogenetic response. We hypothesized that polymorphic differences in genes encoding IFN signal transduction components might account for different patient responses. We studied 174 IFN-treated patients, of whom 79 achieved less than 35% Philadelphia-chromosome (Ph) positive metaphases (responders) and 95 failed to show any cytogenetic response (more than 95% Ph-positive metaphases; non-responders). We compared 17 single nucleotide polymorphisms (SNPs) at IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT3 and STAT5a/b between the two groups and found a significant difference for rs6503691, a SNP tightly linked to STAT5a, STAT5b and STAT3 (minor allele frequency 0.16 for non-responders; 0.06 for responders, P=0.007). Levels of STAT3 mRNA correlated with rs6503691 genotype (P<0.001) as assessed by real time quantitative PCR and therefore we conclude that rs6503691 is associated with the STAT3 expression levels and response of CML patients to IFN

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Contributors

Author: Andrew Chase

Author: Nicholas C.P. Cross

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