title: Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML.
abstract: KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8;21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1).
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jessica.pollard@seattlechildrens.org
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Pollard
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Phoenix A
authors.initials: PA
authors.lastname: Ho
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Yaddanapudi
authors.initials: Y
authors.lastname: Ravindranath
authors.forename: Gary
authors.initials: G
authors.lastname: Dahl
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Lacayo
authors.forename: David
authors.initials: D
authors.lastname: Becton
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Weinstein
authors.forename: Betsy
authors.initials: B
authors.lastname: Hirsch
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: William G
authors.initials: WG
authors.lastname: Woods
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Lange
authors.forename: Craig
authors.initials: C
authors.lastname: Hurwitz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Bernstein
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D050660:Core Binding Factors / Q000235:genetics*; D018572:Disease-Free Survival; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D009154:Mutation; D015995:Prevalence; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050660:Core Binding Factors; D019009:Proto-Oncogene Proteins c-kit