title: An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
abstract: 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.
authors: Laboratory of Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians-Universität, Campus Grosshadern, Germany.
authors: Klaus H
authors: KH
authors: Metzeler
authors: Manuela
authors: M
authors: Hummel
authors: Clara D
authors: CD
authors: Bloomfield
authors: Karsten
authors: K
authors: Spiekermann
authors: Jan
authors: J
authors: Braess
authors: Maria-Cristina
authors: MC
authors: Sauerland
authors: Achim
authors: A
authors: Heinecke
authors: Michael
authors: M
authors: Radmacher
authors: Guido
authors: G
authors: Marcucci
authors: Susan P
authors: SP
authors: Whitman
authors: Kati
authors: K
authors: Maharry
authors: Peter
authors: P
authors: Paschka
authors: Richard A
authors: RA
authors: Larson
authors: Wolfgang E
authors: WE
authors: Berdel
authors: Thomas
authors: T
authors: Büchner
authors: Bernhard
authors: B
authors: Wörmann
authors: Ulrich
authors: U
authors: Mansmann
authors: Wolfgang
authors: W
authors: Hiddemann
authors: Stefan K
authors: SK
authors: Bohlander
authors: Christian
authors: C
authors: Buske
mesh_terms: 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
chemical_list: 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