title: inv(16)/t(16;16) acute myeloid leukemia with non-type A CBFB-MYH11 fusions associate with distinct clinical and genetic features and lack KIT mutations.
abstract: The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in multiple CBFB-MYH11 fusion transcripts, with type A being most frequent. The biologic and prognostic implications of different fusions are unclear. We analyzed CBFB-MYH11 fusion types in 208 inv(16)/t(16;16) patients with de novo disease, and compared clinical and cytogenetic features and the KIT mutation status between type A (n = 182; 87%) and non-type A (n = 26; 13%) patients. At diagnosis, non-type A patients had lower white blood counts (P = .007), and more often trisomies of chromosomes 8 (P = .01) and 21 (P < .001) and less often trisomy 22 (P = .02). No patient with non-type A fusion carried a KIT mutation, whereas 27% of type A patients did (P = .002). Among the latter, KIT mutations conferred adverse prognosis; clinical outcomes of non-type A and type A patients with wild-type KIT were similar. We also derived a fusion-type-associated global gene-expression profile. Gene Ontology analysis of the differentially expressed genes revealed-among others-an enrichment of up-regulated genes involved in activation of caspase activity, cell differentiation and cell cycle control in non-type A patients. We conclude that non-type A fusions associate with distinct clinical and genetic features, including lack of KIT mutations, and a unique gene-expression profile.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Colin G
authors.initials: CG
authors.lastname: Edwards
authors.forename: Deedra
authors.initials: D
authors.lastname: Nicolet
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Eisfeld
authors.forename: Pia
authors.initials: P
authors.lastname: Hoellerbauer
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: John
authors.initials: J
authors.lastname: Curfman
authors.forename: Jessica
authors.initials: J
authors.lastname: Kohlschmidt
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Prior
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pettenati
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D007446:Chromosome Inversion; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D059467:Transcriptome; D055815:Young Adult
chemical_list: C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion; D019009:Proto-Oncogene Proteins c-kit