An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML.
Metzeler
Klaus H
KH
Laboratory of Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians-Universität, Campus Grosshadern, Germany.
Hummel
Manuela
M
Bloomfield
Clara D
CD
Spiekermann
Karsten
K
Braess
Jan
J
Sauerland
Maria-Cristina
MC
Heinecke
Achim
A
Radmacher
Michael
M
Marcucci
Guido
G
Whitman
Susan P
SP
Maharry
Kati
K
Paschka
Peter
P
Larson
Richard A
RA
Berdel
Wolfgang E
WE
Büchner
Thomas
T
Wörmann
Bernhard
B
Mansmann
Ulrich
U
Hiddemann
Wolfgang
W
Bohlander
Stefan K
SK
Buske
Christian
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015342:DNA Probes / Q000737:chemistry / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011237:Predictive Value of Tests; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis / Q000235:genetics
D015342:DNA Probes; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3