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.
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.
Chen
Chien-Yuan
CY
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Lin
Liang-In
LI
Tang
Jih-Luh
JL
Ko
Bo-Sheng
BS
Tsay
Woei
W
Chou
Wen-Chien
WC
Yao
Ming
M
Wu
Shang-Ju
SJ
Tseng
Mei-Hsuan
MH
Tien
Hwei-Fang
HF
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
D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C493728:RUNX1 protein, human