title: A genome-wide single-nucleotide polymorphism-array can improve the prognostic stratification of the core binding factor acute myeloid leukemia.
abstract: Core binding factor (CBF) AML with the D816 C-KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C-KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP-A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome-wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP-A and/or MC was worse than those without lesions in terms of the 2-year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event-free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia-free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C-KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP-A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP-A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C-KIT mutation.
authors.affiliation: Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Jungwon
authors.initials: J
authors.lastname: Huh
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Myung Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Won
authors.forename: Yeung Chul
authors.initials: YC
authors.lastname: Mun
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Min
authors.forename: Dong Hwan Dennis
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D007446:Chromosome Inversion; D050660:Core Binding Factors / Q000235:genetics*; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012074:Remission Induction; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D050660:Core Binding Factors; D009363:Neoplasm Proteins; D003561:Cytarabine; C015019:enocitabine; D019009:Proto-Oncogene Proteins c-kit; D015255:Idarubicin