Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia.
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
H A
HA
Hou
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
C C
CC
Lin
1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
W C
WC
Chou
Biostatistics Consulting Laboratory, School of Nursing and Center of General Education, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
C Y
CY
Liu
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
C Y
CY
Chen
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
J L
JL
Tang
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Y J
YJ
Lai
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
M H
MH
Tseng
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
C F
CF
Huang
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Y C
YC
Chiang
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
F Y
FY
Lee
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Y Y
YY
Kuo
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
M C
MC
Lee
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
M C
MC
Liu
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
C W
CW
Liu
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
L I
LI
Lin
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
M
M
Yao
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
S Y
SY
Huang
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
B S
BS
Ko
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
S C
SC
Hsu
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
S J
SJ
Wu
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
W
W
Tsay
1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Y C
YC
Chen
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
H F
HF
Tien
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D012307:Risk Factors; D055815:Young Adult