title: New prognostic markers, determined using gene expression analyses, reveal two distinct subtypes of chronic myelomonocytic leukaemia patients.
abstract: Chronic myelomonocytic leukaemia (CMML) is a heterogeneous haematopoietic disorder characterized by myeloproliferative or myelodysplastic features. At present, the pathogenesis of this malignancy is not completely understood. In this study, we sought to analyse gene expression profiles of CMML in order to characterize new molecular outcome predictors. A learning set of 32 untreated CMML patients at diagnosis was available for TaqMan low-density array gene expression analysis. From 93 selected genes related to cancer and cell cycle, we built a five-gene prognostic index after multiplicity correction. Using this index, we characterized two categories of patients with distinct overall survival (94% vs. 19% for good and poor overall survival, respectively; P = 0·007) and we successfully validated its strength on an independent cohort of 21 CMML patients with Affymetrix gene expression data. We found no specific patterns of association with traditional prognostic stratification parameters in the learning cohort. However, the poor survival group strongly correlated with high-risk treated patients and transformation to acute myeloid leukaemia. We report here a new multigene prognostic index for CMML, independent of the gene expression measurement method, which could be used as a powerful tool to predict clinical outcome and help physicians to evaluate criteria for treatments.
authors.affiliation: Groupe d'études des transcriptomes, Université Montpellier 2, Centre de Recherche en Biochimie Macromoléculaire, Montpellier, France.
authors.forename: Elias
authors.initials: E
authors.lastname: Bou Samra
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.forename: Fabienne
authors.initials: F
authors.lastname: Vacheret
authors.forename: Ken
authors.initials: K
authors.lastname: Mills
authors.forename: Florence
authors.initials: F
authors.lastname: Rufflé
authors.forename: Jean
authors.initials: J
authors.lastname: Chiesa
authors.forename: David
authors.initials: D
authors.lastname: Piquemal
authors.forename: Anthony
authors.initials: A
authors.lastname: Boureux
authors.forename: Thierry
authors.initials: T
authors.lastname: Lavabre-Bertrand
authors.forename: Eric
authors.initials: E
authors.lastname: Jourdan
authors.forename: Thérèse
authors.initials: T
authors.lastname: Commes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D016896:Treatment Outcome; D020298:U937 Cells
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm