Identification of new classes among acute myelogenous leukaemias with normal karyotype using gene expression profiling

被引:41
作者
Vey, N
Mozziconacci, MJ
Groulet-Martinec, A
Debono, S
Finetti, P
Carbuccia, N
Beillard, E
Devilard, E
Arnoulet, C
Coso, D
Sainty, D
Xerri, L
Stoppa, AM
Lafage-Pochitaloff, M
Nguyen, C
Houlgatte, R
Blaise, D
Maraninchi, D
Birg, F
Birnbaum, D
Bertucci, F
机构
[1] Inst J Paoli I Calmettes, INSERM, UMR599, Dept Mol Oncol,Marseille Canc Inst, F-13009 Marseille, France
[2] Inst J Paoli I Calmettes, INSERM, UMR599, Dept Haematol,Marseille Canc Inst, F-13009 Marseille, France
[3] Inst J Paoli I Calmettes, INSERM, UMR599, Dept Biopathol,Marseille Canc Inst, F-13009 Marseille, France
[4] IPSOGEN SAS, Marseille, France
[5] ERT MEIDIA, Marseille, France
[6] Univ Mediterranee, Marseille, France
[7] ERM206, Marseille, France
关键词
acute myelogenous leukaemia; gene expression; DNA microarrays; chemotherapy; normal karyotype; FLT3;
D O I
10.1038/sj.onc.1207910
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Conventional cytogenetic analysis currently stratifies acute myelogenous leukaemia (AML) into prognostically relevant groups. However, approximately 50% of adult AMLs have normal cytogenetics (NC-AMLs), and represent a heterogeneous and poorly understood group. We analysed gene expression in 55 AML samples including 53 cases from adult patients with NC-AML (n=36), trisomy 8, t(15;17), t(8;21), t(11;19), 7q deletion, and two cell lines using 9000-gene DNA microarrays. Global hierarchical clustering showed that NC-AMLs are a heterogeneous group. Supervised analysis distinguished two subgroups of NC-AML: one subgroup constituted a homogeneous NC cluster ('pure NC-AML'), and the other NC-AMLs were close to the AML cases with translocations ('translocation like'). Gene expression signatures were also derived for patients with trisomy 8, as well as FLT3 and MLL gene duplications. Importantly, samples from 24 NC-AML patients who could be evaluated for clinical outcome were analysed. In all, 43 genes that discriminated two classes of patients with significantly different prognosis were identified. The poor prognosis class contained a majority of 'pure NC-AMLs', whereas the 'translocation-like' AMLs were in the good prognosis class. Discriminator genes included genes involved in drug resistance (TOP2B), protein transport (MTX2, SLC35A2), and cell signalling (MAPK1, PRKAB2). Our results demonstrate the transcriptional heterogeneity of NC-AMLs, and suggest the existence of 'translocation-like' NC-AMLs and of a gene expression signature that may predict response to chemotherapy.
引用
收藏
页码:9381 / 9391
页数:11
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