title: A gene expression based predictor for high risk myeloma treated with intensive therapy and autologous stem cell rescue.
abstract: Myeloma is characterized by a highly variable clinical outcome. Despite the effectiveness of high-dose therapy, 15% of patients relapse within 1 year. We show that these cases also have a significantly shorter post-relapse survival compared to the others (median 14.9 months vs. 40 months, p = 8.03 × 10(- 14)). There are no effective approaches to define this potentially distinct biological group such that treatment could be altered. In this work a series of uniformly treated patients with myeloma were used to develop a gene expression profiling (GEP)-based signature to identify this high risk clinical behavior. Gene enrichment analyses applied to the top differentially expressed genes showed a significant enrichment of epigenetic regulators as well as "stem cell" myeloma genes. A derived 17-gene signature effectively identifies patients at high risk of early relapse as well as impaired overall survival. Integrative genomic analyses showed that epigenetic mechanisms may play an important role on transcription of these genes.
authors.affiliation: Section of Haemato-Oncology.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Brian A
authors.initials: BA
authors.lastname: Walker
authors.forename: Annemiek
authors.initials: A
authors.lastname: Broyl
authors.forename: Martin
authors.initials: M
authors.lastname: Kaiser
authors.forename: David C
authors.initials: DC
authors.lastname: Johnson
authors.forename: Rowan
authors.initials: R
authors.lastname: Kuiper
authors.forename: Mark
authors.initials: M
authors.lastname: van Duin
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Daniel
authors.initials: D
authors.lastname: Brewer
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics* / Q000628:therapy*; D012008:Recurrence; D012306:Risk; D033581:Stem Cell Transplantation; D059467:Transcriptome / Q000502:physiology*; D014182:Transplantation, Autologous
keywords: Myeloma; gene expression profiling; predictor; risk