title: Identification of pluripotent and adult stem cell genes unrelated to cell cycle and associated with poor prognosis in multiple myeloma.
abstract: Gene expression-based scores used to predict risk in cancer frequently include genes coding for DNA replication, repair or recombination. Using two independent cohorts of 206 and 345 previously-untreated patients with Multiple Myeloma (MM), we identified 50 cell cycle-unrelated genes overexpressed in multiple myeloma cells (MMCs) compared to normal human proliferating plasmablasts and non-proliferating bone marrow plasma cells and which have prognostic value for overall survival. Thirty-seven of these 50 myeloma genes (74%) were enriched in genes overexpressed in one of 3 normal human stem cell populations--pluripotent (18), hematopoietic (10) or mesenchymal stem cells (9)--and only three genes were enriched in one of 5 populations of differentiated cells (memory B lymphocytes, T lymphocytes, polymorphonuclear cells, monocytes, osteoclasts). These 37 genes shared by MMCs and adult or pluripotent stem cells were used to build a stem cell score ((SC)score), which proved to be strongly prognostic in the 2 independent cohorts of patients compared to other gene expression-based risk scores or usual clinical scores using multivariate Cox analysis. This finding highlights cell cycle-unrelated prognostic genes shared by myeloma cells and normal stem cells, whose products might be important for normal and malignant stem cell biology.
authors.affiliation: INSERM, U1040, Montpellier, France.
authors.forename: Alboukadel
authors.initials: A
authors.lastname: Kassambara
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.forename: Jennifer
authors.initials: J
authors.lastname: Torrent
authors.forename: Jean François
authors.initials: JF
authors.lastname: Rossi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D053687:Adult Stem Cells / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis