title: Gene mutation patterns in patients with minimally differentiated acute myeloid leukemia.
abstract: Minimally differentiated acute myeloid leukemia (AML-M0) is a rare subtype of AML with poor prognosis. Although genetic alterations are increasingly reported in AML, the gene mutations have not been comprehensively studied in AML-M0. We aimed to examine a wide spectrum of gene mutations in patients with AML-M0 to determine their clinical relevance. Twenty gene mutations including class I, class II, class III of epigenetic regulators (IDH1, IDH2, TET2, DNMT3A, MLL-PTD, ASXL1, and EZH2), and class IV (tumor suppressor genes) were analyzed in 67 patients with AML-M0. Mutational analysis was performed with polymerase chain reaction-based assays followed by direct sequencing. The most frequent gene mutations from our data were FLT3-ITD/FLT3-TKD (28.4%), followed by mutations in IDH1/IDH2 (28.8%), RUNX1 (23.9%), N-RAS/K-RAS (12.3%), TET2 (8.2%), DNMT3A (8.1%), MLL-PTD (7.8%), and ASXL1 (6.3%). Seventy-nine percent (53/67) of patients had at least one gene mutation. Class I genes (49.3%) were the most common mutated genes, which were mutually exclusive. Class III genes of epigenetic regulators were also frequent (43.9%). In multivariate analysis, old age [hazard ratio (HR) 1.029, 95% confidence interval (CI) 1.013-1.044, P=.001) was the independent adverse factor for overall survival, and RUNX1 mutation (HR 2.326, 95% CI 0.978-5.533, P=.056) had a trend toward inferior survival. In conclusion, our study showed a high frequency of FLT3, RUNX1, and IDH mutations in AML-M0, suggesting that these mutations played a role in the pathogenesis and served as potential therapeutic targets in this rare and unfavorable subtype of AML.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Kao
authors.affiliation: Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Liang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Jin-Hou
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Kuo
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Po-Nan
authors.initials: PN
authors.lastname: Wang
authors.affiliation: Division of Pediatric Hematology-Oncology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Yang
authors.affiliation: Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Shih
authors.affiliation: Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tung-Huei
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Chang Gung University, Taoyuan, Taiwan. Electronic address: sly7012@adm.cgmh.org.tw.
authors.forename: Lee-Yung
authors.initials: LY
authors.lastname: Shih
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D007223:Infant; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D060787:Neoplasm Grading; D063868:Patient Outcome Assessment; D055815:Young Adult