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Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric/adult AML: a report from the Children's Oncology Group and SWOG

Phoenix A. Ho, Kenneth J. Kopecky, Todd A. Alonzo, Robert B. Gerbing, Kristen L. Miller, Julia Kuhn, Rong Zeng, Rhonda E. Ries, Susana C. Raimondi, Betsy A. Hirsch, Vivian Oehler, Craig A. Hurwitz, Janet L. Franklin, Alan S. Gamis, Stephen H. Petersdorf, Jeanne E. Anderson, John E. Godwin, Gregory H. Reaman, Cheryl L. Willman, Irwin D. Bernstein, Jerald P. Radich, Frederick R. Appelbaum, Derek L. Stirewalt and Soheil Meshinchi

Abstract

The IDH1 SNP rs11554137 was recently reported in association with poor prognosis in normal karyotype adult AML. We aimed to determine the prevalence, clinical associations, and prognostic significance of SNP rs11554137 in unselected pediatric and adult AML patients. Diagnostic marrow specimens from 527 AML patients treated on the pediatric trial COG-AAML03P1 (N=253) or adult SWOG trials (N=274) were analyzed for the presence of the IDH1 SNP. SNP rs11554137 was present in 11% of pediatric and adult AML patients. SNP status had no prognostic impact on survival in pediatric patients. In adult AML, overall survival (OS) from study entry for SNP-positive patients was 10% vs. 18% for SNP-negative patients (P=0.44). Among the 142 adult patients who achieved complete remission (CR), 5 year relapse-free survival (RFS) was significantly worse for SNP-positive patients (0% vs. 25%, P=0.0014). However, among adult patients with normal cytogenetics, FLT3/ITD was present in 90% of SNP-positive patients vs. 59% of SNP-negative patients (P=0.0053). Thus in multivariate analysis, adjusting for the effects of age, cytogenetics, and FLT3/ITD, the independent prognostic effect of SNP positivity was not statistically significant (HR=1.72, P=0.18). The clinical profile of SNP-positive patients suggests that SNP rs11554137 may have biologic effects which bear further investigation. The clinical trials in this study are registered at http://www.clinicaltrials.gov under NCT000707174 and NCT00899171.

  • Submitted April 20, 2011.
  • Accepted August 13, 2011.