title: Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children's Oncology Group and SWOG.
abstract: IDH1 SNP rs11554137 was recently reported in association with poor prognosis in normal karyotype adult acute myeloid leukemia (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 Children's Oncology Group-AAML03P1 (N = 253) or adult SWOG trials (N = 274) were analyzed for the presence of the SNP. SNP rs11554137 was present in 11% of all patients. SNP status had no prognostic impact on survival in pediatric patients. In adult AML, overall survival for SNP-positive patients was 10% versus 18% for SNP-negative patients (P = .44). Among the 142 adults who achieved complete remission, 5-year relapse-free survival was significantly worse for SNP-positive patients (0% vs 25%, P = .0014). However, among adults with normal cytogenetics, FLT3/ITD was present in 90% of SNP-positive patients versus 59% of SNP-negative patients (P = .0053). In multivariate analysis, adjusting for the effects of age, cytogenetics, and FLT3/ITD, the independent prognostic effect of SNP positivity was not statistically significant (hazard ratio = 1.72, P = .18). The clinical profile of SNP-positive patients suggests that SNP rs11554137 may have biologic effects that bear further investigation. The clinical trials in this study are registered at http://www.clinicaltrials.gov as #NCT000707174 and #NCT00899171.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. pho@fhcrc.org
authors.forename: Phoenix A
authors.initials: PA
authors.lastname: Ho
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kopecky
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Miller
authors.forename: Julia
authors.initials: J
authors.lastname: Kuhn
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Rhonda E
authors.initials: RE
authors.lastname: Ries
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Hirsch
authors.forename: Vivian
authors.initials: V
authors.lastname: Oehler
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hurwitz
authors.forename: Janet L
authors.initials: JL
authors.lastname: Franklin
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Petersdorf
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Anderson
authors.forename: John E
authors.initials: JE
authors.lastname: Godwin
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Bernstein
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000502:physiology; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008495:Medical Oncology / Q000458:organization & administration; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011379:Prognosis; D012955:Societies, Medical; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human