title: A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines.
abstract: BACKGROUND
  Multiple myeloma is a plasma-cell tumor with heterogeneity in molecular abnormalities and treatment response.
  
  
  METHODS
  We have assessed whether human myeloma cell lines have kept patients' heterogeneity using Affymetrix gene expression profiling of 40 human myeloma cell lines obtained with or without IL6 addition and could provide a signature for stratification of patient risk.
  
  
  RESULTS
  Human myeloma cell lines, especially those derived in the presence of IL6, displayed a heterogeneity that overlaps that of the patients with multiple myeloma. Human myeloma cell lines segregated into 6 groups marked by overexpression of MAF, MMSET, CCND1, FRZB with or without overexpression of cancer testis antigens (CTA). Cell lines of CTA/MAF and MAF groups have a translocation involving C-MAF or MAFB, cell lines of groups CCND1-1 and CCND1-2like have a t(11;14) and cell lines of group MMSET have a t(4;14). The CTA/FRZB group comprises cell lines that had no or no recurrent 14q32 translocation. Expression of 248 genes accounted for human myeloma cell line molecular heterogeneity. Human myeloma cell line heterogeneity genes comprise genes with prognostic value for survival of patients making it possible to build a powerful prognostic score involving a total of 13 genes.
  
  
  CONCLUSIONS
  Human myeloma cell lines derived in the presence of IL6 recapitulate the molecular diversity of multiple myeloma that made it possible to design, using human myeloma cell line heterogeneity genes, a high-risk signature for patients at diagnosis. We propose this classification to be used when addressing the physiopathology of multiple myeloma with human myeloma cell lines.
authors.affiliation: 1INSERM, U847, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
authors.forename: Régis
authors.initials: R
authors.lastname: Bataille
authors.forename: Géraldine
authors.initials: G
authors.lastname: Descamps
authors.forename: Sophie
authors.initials: S
authors.lastname: Maïga
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.forename: Michel
authors.initials: M
authors.lastname: Jourdan
authors.forename: Martine
authors.initials: M
authors.lastname: Amiot
authors.forename: Catherine
authors.initials: C
authors.lastname: Pellat-Deceunynck
mesh_terms: D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D005819:Genetic Markers; D015850:Interleukin-6