A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon alpha
A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon alpha
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
STAT3, chronic myeloid leukemia, interferon
148-152
Kreil, Sebastian
bdd3cef1-cffa-4ec7-a783-e183cde237f4
Waghorn, Katherine
60a6a26d-556b-41fc-84ee-dab95d63ab68
Ernst, Thomas
96c7805b-c900-4545-9f93-1a83d789cb56
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
White, Helen
2181c0b9-fc3b-407e-95eb-3510524603e5
Hehlmann, Rudiger
3e2a5d6e-9b68-4675-93ce-44e3f7892493
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Hochhaus, Aandreas
f15bfe40-3746-422b-8fd3-d46e780238dc
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
January 2010
Kreil, Sebastian
bdd3cef1-cffa-4ec7-a783-e183cde237f4
Waghorn, Katherine
60a6a26d-556b-41fc-84ee-dab95d63ab68
Ernst, Thomas
96c7805b-c900-4545-9f93-1a83d789cb56
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
White, Helen
2181c0b9-fc3b-407e-95eb-3510524603e5
Hehlmann, Rudiger
3e2a5d6e-9b68-4675-93ce-44e3f7892493
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Hochhaus, Aandreas
f15bfe40-3746-422b-8fd3-d46e780238dc
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
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), .
(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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Published date: January 2010
Keywords:
STAT3, chronic myeloid leukemia, interferon
Identifiers
Local EPrints ID: 71985
URI: http://eprints.soton.ac.uk/id/eprint/71985
ISSN: 0390-6078
PURE UUID: 9e781618-6e3c-408f-9e5a-0a3549bc5705
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Date deposited: 14 Jan 2010
Last modified: 14 Mar 2024 02:46
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Author:
Sebastian Kreil
Author:
Katherine Waghorn
Author:
Thomas Ernst
Author:
Helen White
Author:
Rudiger Hehlmann
Author:
Andreas Reiter
Author:
Aandreas Hochhaus
Corporate Author: German CML Study Group
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