SF3B1 mutations in patients with myelodysplastic syndromes: the mutation is stable during disease evolution.
The SF3B1 mutation can be detected in patients with myelodysplastic syndrome (MDS), but the report regarding the association of this mutation with other genetic alterations and its stability during disease progression is limited. In this study, SF3B1 mutations were identified in 10% of total cohort of 479 MDS patients and 61.8% of 34 patients with refractory anemia with ring sideroblasts (RARS). SF3B1 mutations were closely associated with older age, higher platelet counts, lower lactate dehydrogenase levels, good-risk cytogenetics, and mutations of DNMT3A, but inversely related to ASXL1 mutations. Most SF3B1-mutated patients had concurrent other genetic alterations, including DNMT3A and RUNX1 mutations. There was no prognostic difference between patients with SF3B1 mutations and those without. Sequential studies in 417 samples from 142 patients demonstrated that all SF3B1-mutated patients retained the same mutations during disease evolution with the exception of two patients who lost the mutation after allogeneic hematopoietic stem cell transplantation, whereas none of the SF3B1-wild patients acquired a novel mutation during clinical follow-ups. In conclusion, the patients with SF3B1 mutations had distinct clinic-biologic features. SF3B1 mutations, accompanied with other genetic alterations, especially DNMT3A mutations, may play a role in the development of MDS, but have little role in disease progression.
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chien-Chin
CC
Lin
Hsin-An
HA
Hou
Wen-Chien
WC
Chou
Yuan-Yeh
YY
Kuo
Shang-Ju
SJ
Wu
Chieh-Yu
CY
Liu
Chien-Yuan
CY
Chen
Mei-Hsuan
MH
Tseng
Chi-Fei
CF
Huang
Fen-Yu
FY
Lee
Ming-Chih
MC
Liu
Chia-Wen
CW
Liu
Jih-Luh
JL
Tang
Ming
M
Yao
Shang-Yi
SY
Huang
Szu-Chun
SC
Hsu
Bor-Sheng
BS
Ko
Woei
W
Tsay
Yao-Chang
YC
Chen
Hwei-Fang
HF
Tien
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D018450:Disease Progression; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D000072260:RNA Splicing Factors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics* / Q000378:metabolism
C473949:ASXL1 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C000717967:DNMT3A protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; C493728:RUNX1 protein, human; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D007770:L-Lactate Dehydrogenase; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A