Quantitative analysis of CKS1B mRNA expression and copy number gain in patients with plasma cell disorders

被引:11
作者
Stella, Flavia [1 ]
Pedrazzini, Estela [1 ,4 ]
Baialardo, Edgardo [2 ]
Fantl, Dorotea Beatriz [3 ]
Schutz, Natalia [3 ]
Slavutsky, Irma [1 ]
机构
[1] Acad Nacl Med Buenos Aires, CONICET, Inst Expt Med, Lab Genet Neoplasias Linfoides, Buenos Aires, DF, Argentina
[2] Ctr Estudios Genet, Buenos Aires, DF, Argentina
[3] Hosp Italian, Dept Clin Med, Secc Hematol, Buenos Aires, DF, Argentina
[4] Univ Nacl Noroeste Prov Buenos Aires UNNOBA, Buenos Aires, DF, Argentina
关键词
Multiple myeloma; MGUS; CKS1B gene expression; FISH; MULTIPLE-MYELOMA PATIENTS; IN-SITU HYBRIDIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; RETRACTED ARTICLE. SEE; HIGH-DOSE CHEMOTHERAPY; CHROMOSOME BAND 1Q21; PROGNOSTIC VALUE; RISK-STRATIFICATION; PERICENTROMERIC HETEROCHROMATIN; NUCLEAR EXPRESSION;
D O I
10.1016/j.bcmd.2014.05.006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In this study, we have examined CKS1B gene expression and copy number in a total of 114- patients at diagnosis: 83 with multiple myeloma (MM) and 31 with monoclonal gammopathy of undetermined significance (MGUS). Results were correlated with cytogenetics, FISH and clinical characteristic. Significant CKS1B mRNA levels in MM compared to MGUS cases (p < 0.048) were detected. In MM, the frequency of 1q21 (CKS1B) copy gain was significantly higher in cases with abnormal karyotype compared to patients with normal karyotype (p = 0.021). Global analysis showed a positive correlation between CKS1B expression and 1q21 copy number (p < 0.0001). No association between CKS1B mRNA expression and clinical parameters was found. However, a significantly higher level of beta 2 microglobulin in cases with 1q21 gains than those without (p = 0.0094) was observed. Overall survival was shorter in cases with 1q21 gain compared to those with normal 1q21 region (p = 0.0082). Our results suggest a role for CKS1B in the multiple step process of progression of MGUS to MM and show that CKS1B copy gain has a more significant prognostic value than its overexpression. This adverse impact on survival probably reflects the genetic instability associated to chromosome 1q alterations resulting in a more aggressive behavior of the disease. (C) 2014 Published by Elsevier Inc.
引用
收藏
页码:110 / 117
页数:8
相关论文
共 68 条
  • [1] Differential expression of CKS-1B in typical and blastoid variants of mantle cell lymphoma
    Akyurek, Nalan
    Drakos, Elias
    Giaslakiotis, Konstantinos
    Knoblock, Ronald J.
    Abruzzo, Lynne V.
    Ning, Yi
    Rassidakis, Georgios Z.
    Medeiros, L. Jeffrey
    [J]. HUMAN PATHOLOGY, 2010, 41 (10) : 1448 - 1455
  • [2] Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value
    An, Gang
    Xu, Yan
    Shi, Lihui
    Zhong, Shizhen
    Deng, Shuhui
    Xie, Zhenqing
    Sui, Weiwei
    Zhan, Fenghuang
    Qiu, Lugui
    [J]. HAEMATOLOGICA, 2014, 99 (02) : 353 - 359
  • [3] Genomic aberrations in anaplastic multiple myeloma: High frequency of 1q21(CKS1B) amplifications
    Bahmanyar, Mohammad
    Qi, Xiaoying
    Chang, Hong
    [J]. LEUKEMIA RESEARCH, 2013, 37 (12) : 1726 - 1728
  • [4] Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
    Bianchini, Michele
    De Brasi, Carlos
    Gargallo, Patricia
    Gonzalez, Mariana
    Bengio, Raquel
    Larripa, Irene
    [J]. EUROPEAN JOURNAL OF HAEMATOLOGY, 2009, 82 (04) : 292 - 300
  • [5] Mapping of Chromosome 1p Deletions in Myeloma Identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as Being Genes in Regions Associated with Adverse Survival
    Boyd, Kevin D.
    Ross, Fiona M.
    Walker, Brian A.
    Wardell, Christopher P.
    Tapper, William J.
    Chiecchio, Laura
    Dagrada, GianPaolo
    Konn, Zoe J.
    Gregory, Walter M.
    Jackson, Graham H.
    Child, J. Anthony
    Davies, Faith E.
    Morgan, Gareth J.
    [J]. CLINICAL CANCER RESEARCH, 2011, 17 (24) : 7776 - 7784
  • [6] The SCF ubiquitin ligase: Insights into a molecular machine
    Cardozo, T
    Pagano, M
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (09) : 739 - 751
  • [7] High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients
    Carrasco, DR
    Tonon, G
    Huang, YS
    Zhang, YY
    Sinha, R
    Bin, F
    Stewart, JP
    Zhan, FG
    Khatry, D
    Protopopova, M
    Protopopov, A
    Sukhdeo, K
    Hanamura, I
    Stephens, O
    Barlogie, B
    Anderson, KC
    Chin, L
    Shaughnessy, JD
    Brennan, C
    DePinho, RA
    [J]. CANCER CELL, 2006, 9 (04) : 313 - 325
  • [8] Chang H, 2010, BONE MARROW TRANSPL, V45, P117, DOI 10.1038/bmt.2009.107
  • [9] Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantation
    Chang, Hong
    Qi, Xiaoying
    Trieu, Young
    Xu, Wei
    Reader, Jocelyn C.
    Ning, Yi
    Reece, Donna
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2006, 135 (04) : 486 - 491
  • [10] Impact of genomic aberrations including chromosome 1 abnormalities on the outcome of patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone
    Chang, Hong
    Jiang, Allan
    Qi, Connie
    Trieu, Young
    Chen, Christine
    Reece, Donna
    [J]. LEUKEMIA & LYMPHOMA, 2010, 51 (11) : 2084 - 2091