Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation.
Mutations of nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase gene (IDH1) have been identified in patients with gliomas. Recent genome-wide screening also revealed IDH1 mutation as a recurrent event in acute myeloid leukemia (AML), but its clinical implications in AML are largely unknown. We analyzed 493 adult Chinese AML patients in Taiwan and found 27 patients (5.5%) harboring this mutation. IDH1 mutation was strongly associated with normal karyotype (8.4%, P = .002), isolated monosomy 8 (P = .043), NPM1 mutation (P < .001), and French-American-British M1 subtype (P < .001), but inversely associated with French-American-British M4 subtype (P = .030) and expression of HLA-DR, CD13, and CD14 (P = .002, .003, and .038, respectively). There was no impact of this mutation on patient survival. Sequential analysis of IDH1 mutation was performed in 130 patients during follow-ups. None of the 112 patients without IDH1 mutation at diagnosis acquired this mutation at relapse. In all 18 IDH1-mutated patients studied, the mutation disappeared in complete remission; the same mutation reappeared in all 11 samples obtained at relapse. We conclude that IDH1 is associated with distinct clinical and biologic characteristics and seems to be very stable during disease evolution.
Chou
Wen-Chien
WC
Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
Hou
Hsin-An
HA
Chen
Chien-Yuan
CY
Tang
Jih-Luh
JL
Yao
Ming
M
Tsay
Woei
W
Ko
Bor-Shen
BS
Wu
Shang-Ju
SJ
Huang
Shang-Yi
SY
Hsu
Szu-Chun
SC
Chen
Yao-Chang
YC
Huang
Yen-Ning
YN
Chang
Yi-Chang
YC
Lee
Fen-Yu
FY
Liu
Ming-Chi
MC
Liu
Chia-Wen
CW
Tseng
Mei-Hsuan
MH
Huang
Chi-Fei
CF
Tien
Hwei-Fang
HF
D000328:Adult; D000368:Aged; D018826:CD13 Antigens / Q000096:biosynthesis / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D055106:Genome-Wide Association Study; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D012008:Recurrence; D012074:Remission Induction; D013624:Taiwan
D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D000090243:Nucleophosmin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D018826:CD13 Antigens