title: High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome.
abstract: t(8;21)/RUNX1-RUNX1T1-positive acute myeloid leukemia (AML) is prognostically favorable; however, outcome is heterogeneous. We analyzed 139 patients with t(8;21)/RUNX1-RUNX1T1-positive AML (de novo: n=117; therapy-related: n=22) to determine frequency and prognostic impact of additional genetic abnormalities. All patients were investigated for mutations (mut) in ASXL1, FLT3, KIT, NPM1, MLL, IDH1, IDH2, KRAS, NRAS, CBL and JAK2. Sixty-nine of 139 cases (49.6%) had 1 mutation in addition to RUNX1-RUNX1T1, and 23/139 (16.5%) had ⩾2 additional mutations. Most common were KITmut (23/139; 16.5%), NRASmut (18/139; 12.9%) and ASXL1mut (16/139; 11.5%). FLT3-ITD, FLT3-TKDmut, CBLmut, KRASmut, IDH2mut and JAK2mut were found in 2.9-5.0%. Additional chromosomal abnormalities (ACAs) were found in 97/139 (69.8%). Two-year overall survival (OS) was 73.4% in 111 intensively treated patients. KITD816mut negatively impacted on OS in de novo AML (2-year OS: 59.1% vs 82.0%, P=0.03), ASXL1mut on EFS (de novo AML: 20% vs 59.1%, P=0.011; total cohort: 28.6% vs 56.7%, P=0.021). Sex chromosome loss was favorable (2-year EFS: 66.9% vs 43.0%, P=0.031), whereas +8 was adverse on EFS (2-year EFS: 26.7% vs 55.9%, P=0.02). In conclusion, t(8;21)/RUNX1-RUNX1T1-positive AML shows a high frequency of additional genetic alterations. Investigation for KITD816 and ASXL1mut combined with investigation of ACAs is recommended in t(8;21)/RUNX1-RUNX1T1-positive AML because of the prognostic significance of these parameters.
authors.affiliation: 1] MLL Munich Leukemia Laboratory, Munich, Germany [2] Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria.
authors.forename: M-T
authors.initials: MT
authors.lastname: Krauth
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Eder
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Alpermann
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bacher
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Nadarajah
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Haferlach
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D012008:Recurrence; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C000716967:NPM1 protein, human; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D000090243:Nucleophosmin