title: Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation.
abstract: Using fluorescence in situ hybridization we investigated amplification of chromosome band 1q21 (Amp1q21) in more than 500 untreated patients with monoclonal gammopathy of undetermined significance (MGUS; n = 14), smoldering multiple myeloma (SMM; n = 31), and newly diagnosed MM (n = 479) as well as 45 with relapsed MM. The frequency of Amp1q21 was 0% in MGUS, 45% in SMM, 43% in newly diagnosed MM, and 72% in relapsed MM (newly diagnosed versus relapsed MM, P < .001). Amp1q21 was detected in 10 of 12 patients whose disease evolved to active MM compared with 4 of 19 who remained with SMM (P < .001). Patients with newly diagnosed MM with Amp1q21 had inferior 5-year event-free/overall survival compared with those lacking Amp1q21 (38%/52% versus 62%/78%, both P < .001). Thalidomide improved 5-year EFS in patients lacking Amp1q21 but not in those with Amp1q21 (P = .004). Multivariate analysis including other major predictors revealed that Amp1q21 was an independent poor prognostic factor. Relapsed patients who had Amp1q21 at relapse had inferior 5-year postrelapse survival compared with those lacking Amp1q21 at relapse (15% versus 53%, P = .027). The proportion of cells with Amp1q21 and the copy number of 1q21 tended to increase at relapse compared with diagnosis. Our data suggest that Amp1q21 is associated with both disease progression and poor prognosis.
authors.affiliation: Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W. Markham St. #776, Little Rock, AR 72205, USA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hanamura
authors.forename: James P
authors.initials: JP
authors.lastname: Stewart
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Huang
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Madhumita
authors.initials: M
authors.lastname: Santra
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Sawyer
authors.forename: Klaus
authors.initials: K
authors.lastname: Hollmig
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangarri
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pineda-Roman
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Bart
authors.initials: B
authors.lastname: Burington
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
mesh_terms: D000368:Aged; D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality; D010265:Paraproteinemias / Q000235:genetics*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome