title: Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.
abstract: We previously reported the adverse prognostic impact of Wilms tumor 1 gene (WT1) mutations in younger adult cytogenetically normal acute myeloid leukemia (CN-AML). Here, we investigated 243 older (> or = 60 years) primary CN-AML patients. WT1 mutated (WT1mut) patients (7%) had FLT3-ITD more frequently (P < .001), lower hemoglobin (P = .01), higher white blood cell count (P = .03) and percentage blood blasts (P = .03), and a shorter overall survival (P = .08) than WT1 wild-type (WT1wt) patients. Comparing older and younger WT1mut patients, they had similar pretreatment characteristics and outcome. By contrast, among WT1wt CN-AML, younger patients had a significantly better outcome. A WT1 mutation-associated gene-expression signature, reported here for the first time, included CD96, a leukemia stem cell-specific marker, and genes involved in gene regulation (eg, MLL, PML, and SNRPN) and in proliferative and metabolic processes (eg, INSR, IRS2, and PRKAA1), supporting the role of mutated WT1 in deregulating multiple homeostatic processes. Our results indicate that WT1mut CN-AML represents a distinct entity with poor treatment response across age groups. This study has been registered at www.clinicaltrials.gov as #NCT00900224.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Dean
authors.initials: D
authors.lastname: Margeson
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Kelsi B
authors.initials: KB
authors.lastname: Holland
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Carter
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D016162:Genes, Wilms Tumor; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins