4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Haematologica, Vol 95, Issue 1, 148-152 doi:10.3324/haematol.2009.011510
Copyright © 2010 by Ferrata Storti Foundation
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Chronic Myeloid Leukemia

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

Sebastian Kreil1,3, Katherine Waghorn1,2, Thomas Ernst1,3, Andrew Chase1,2, Helen White1, Rüdiger Hehlmann3, Andreas Reiter3, Andreas Hochhaus3, Nicholas C.P. Cross1,2 on behalf of the German CML Study Group

1 Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK
2 Human Genetics Division, University of Southampton School of Medicine, Southampton, UK
3 III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Germany

Correspondence: Nicholas C.P. Cross, Wessex Regional Genetics Laboratory, Salisbury District Hospital Salisbury, SP2 8BJ, UK. E-mail: ncpc{at}soton.ac.uk

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.

Key words: STAT3, chronic myeloid leukemia, interferon.