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.
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.
Hanamura
Ichiro
I
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.
Stewart
James P
JP
Huang
Yongsheng
Y
Zhan
Fenghuang
F
Santra
Madhumita
M
Sawyer
Jeffrey R
JR
Hollmig
Klaus
K
Zangarri
Maurizio
M
Pineda-Roman
Mauricio
M
van Rhee
Frits
F
Cavallo
Federica
F
Burington
Bart
B
Crowley
John
J
Tricot
Guido
G
Barlogie
Bart
B
Shaughnessy
John D
JD
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