title: Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction.
abstract: 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.
authors.affiliation: Department of Pathology, University of New Mexico (UNM), Albuquerque, 87131, USA.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Wilson
authors.forename: George S
authors.initials: GS
authors.lastname: Davidson
authors.forename: Shawn B
authors.initials: SB
authors.lastname: Martin
authors.forename: Erik
authors.initials: E
authors.lastname: Andries
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Potter
authors.forename: Richard
authors.initials: R
authors.lastname: Harvey
authors.forename: Kerem
authors.initials: K
authors.lastname: Ar
authors.forename: Yuexian
authors.initials: Y
authors.lastname: Xu
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kopecky
authors.forename: Donna P
authors.initials: DP
authors.lastname: Ankerst
authors.forename: Holly
authors.initials: H
authors.lastname: Gundacker
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Slovak
authors.forename: Monica
authors.initials: M
authors.lastname: Mosquera-Caro
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Chen
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Maurice
authors.initials: M
authors.lastname: Murphy
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schultz
authors.forename: Huining
authors.initials: H
authors.lastname: Kang
authors.forename: Xuefei
authors.initials: X
authors.lastname: Wang
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Susan R
authors.initials: SR
authors.lastname: Atlas
authors.forename: John
authors.initials: J
authors.lastname: Godwin
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
mesh_terms: 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
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin