Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction.
To determine whether gene expression profiling could improve risk classification and outcome prediction in older acute myeloid leukemia (AML) patients, expression profiles were obtained in pretreatment leukemic samples from 170 patients whose median age was 65 years. Unsupervised clustering methods were used to classify patients into 6 cluster groups (designated A to F) that varied significantly in rates of resistant disease (RD; P < .001), complete response (CR; P = .023), and disease-free survival (DFS; P = .023). Cluster A (n = 24), dominated by NPM1 mutations (78%), normal karyotypes (75%), and genes associated with signaling and apoptosis, had the best DFS (27%) and overall survival (OS; 25% at 5 years). Patients in clusters B (n = 22) and C (n = 31) had the worst OS (5% and 6%, respectively); cluster B was distinguished by the highest rate of RD (77%) and multidrug resistant gene expression (ABCG2, MDR1). Cluster D was characterized by a "proliferative" gene signature with the highest proportion of detectable cytogenetic abnormalities (76%; including 83% of all favorable and 34% of unfavorable karyotypes). Cluster F (n = 33) was dominated by monocytic leukemias (97% of cases), also showing increased NPM1 mutations (61%). These gene expression signatures provide insights into novel groups of AML not predicted by traditional studies that impact prognosis and potential therapy.
Wilson
Carla S
CS
Department of Pathology, University of New Mexico (UNM), Albuquerque, 87131, USA.
Davidson
George S
GS
Martin
Shawn B
SB
Andries
Erik
E
Potter
Jeffrey
J
Harvey
Richard
R
Ar
Kerem
K
Xu
Yuexian
Y
Kopecky
Kenneth J
KJ
Ankerst
Donna P
DP
Gundacker
Holly
H
Slovak
Marilyn L
ML
Mosquera-Caro
Monica
M
Chen
I-Ming
IM
Stirewalt
Derek L
DL
Murphy
Maurice
M
Schultz
Frederick A
FA
Kang
Huining
H
Wang
Xuefei
X
Radich
Jerald P
JP
Appelbaum
Frederick R
FR
Atlas
Susan R
SR
Godwin
John
J
Willman
Cheryl L
CL
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D016000:Cluster Analysis; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D018570:Risk Assessment; D015398:Signal Transduction / Q000235:genetics
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin