title: Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG).
abstract: In this study, we evaluated the impact of secondary genetic lesions in acute myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11. We studied 176 patients, all enrolled on prospective treatment trials, for secondary chromosomal aberrations and mutations in N-/KRAS, KIT, FLT3, and JAK2 (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT (37%) and FLT3 (17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary genetic lesions influenced achievement of complete remission. In multivariable analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04], log(10)(WBC) (HR = 1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006), trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14) revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations were mainly attributed to exon 8 and tyrosine kinase domain mutations, respectively. Our large study emphasizes the impact of both secondary chromosomal aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).
authors.affiliation: Universitätsklinikum Ulm, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Verena I
authors.initials: VI
authors.lastname: Gaidzik
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Corbacioglu
authors.forename: Daniela
authors.initials: D
authors.lastname: Späth
authors.forename: Sabine
authors.initials: S
authors.lastname: Kayser
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Köhne
authors.forename: Gerhard
authors.initials: G
authors.lastname: Held
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Heinz
authors.initials: H
authors.lastname: Kirchen
authors.forename: Mathias
authors.initials: M
authors.lastname: Rummel
authors.forename: Katharina
authors.initials: K
authors.lastname: Götze
authors.forename: Heinz-August
authors.initials: HA
authors.lastname: Horst
authors.forename: Mark
authors.initials: M
authors.lastname: Ringhoffer
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Mohammed
authors.initials: M
authors.lastname: Wattad
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Salih
authors.forename: Andrea
authors.initials: A
authors.lastname: Kündgen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics* / Q000648:ultrastructure; D002892:Chromosomes, Human, Pair 22; D002898:Chromosomes, Human, Pair 8; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D005260:Female; D011905:Genes, ras; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D014314:Trisomy; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3