title: RUNX1 gene mutation in primary myelodysplastic syndrome--the mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome.
abstract: Mutations of Runt-related transcription factor 1 (RUNX1) have been detected in patients with myelodysplastic syndrome (MDS). However, the prognostic implication of RUNX1 mutations in primary MDS is limited. The stage of the disease at which the mutations are acquired and whether they persist during the disease course also remain unclear. We analysed mutations of RUNX1 exons 3-8 in 132 patients with primary MDS and correlated the results with clinical features. Serial studies were performed during the follow-up period. Sixteen patients (12%) had RUNX1 mutations at the time of diagnosis. All RUNX1 mutations that were detected at diagnosis remained unchanged during the clinical course. Two other patients acquired RUNX1 mutations at leukaemic transformation 34 months and 35 months after the diagnosis of MDS. Patients with RUNX1 mutations at diagnosis had higher neutrophil counts and higher frequency of -7/7q deletion than those without. Furthermore, RUNX1 mutation was closely associated with a short overall survival (P = 0.039). This is the first report to demonstrate that RUNX1 mutation can not only be detected early at diagnosis but also acquired during disease progression and is associated with poor prognosis in patients with primary MDS. It may play a role in the development and progression of a subset of primary MDS.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Bo-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C493728:RUNX1 protein, human