Chang Hong, Qi Xiaoying, Trieu Young, Xu Wei, Reader Jocelyn C, Ning Yi, Reece Donna
Department of Laboratory Hematology, Toronto General Hospital, University Health Network, Toronto, Canada.
Br J Haematol. 2006 Nov;135(4):486-91. doi: 10.1111/j.1365-2141.2006.06325.x. Epub 2006 Sep 22.
The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM) patients treated with intensive chemotherapy followed by autologous stem cell transplantation. CKS1B amplification (3-8 CKS1B signals) was detected in 31of 99 (31%) patients and was associated with deletions of p53 (P = 0.003) and 13q (P = 0.039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was associated with bone marrow plasmacytosis (P = 0.02), but there was no correlation with patient age, gender, disease stage, lytic bone lesions, albumin, creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with CKS1B amplification had a significantly shorter progression-free survival than those without such amplification (18.5 vs. 25.7 months, P = 0.035). Likewise, a shorter overall survival (44.8 months vs. not reached) was observed; however, the difference did not reach statistical significance (P = 0.20). Seven patients had paired bone marrows obtained at diagnosis and at relapse, the percentage of cells with CKS1B amplification and the level of amplification were significantly increased in the relapse marrows. In this cohort of patients, CKS1B was frequently amplified in MM and may represent genetic instability associated with disease progression.
通过间期荧光原位杂交技术,对99例接受强化化疗后行自体干细胞移植的多发性骨髓瘤(MM)患者进行研究,以探讨1q21区域CKS1B(细胞周期蛋白激酶亚基1B)基因反复扩增的发生率及其预后相关性。在99例患者中的31例(31%)检测到CKS1B扩增(3 - 8个CKS1B信号),其与p53缺失(P = 0.003)和13q缺失(P = 0.039)相关,但与易位t(11;14)或t(4;14)无关。CKS1B扩增与骨髓浆细胞增多症相关(P = 0.02),但与患者年龄、性别、疾病分期、溶骨性骨病变、白蛋白、肌酐、C反应蛋白或β2微球蛋白水平无关。CKS1B扩增的患者无进展生存期明显短于无扩增的患者(18.5个月对25.7个月,P = 0.035)。同样,观察到总生存期较短(44.8个月对未达到);然而,差异未达到统计学意义(P = 0.20)。7例患者在诊断和复发时获取了配对的骨髓,复发骨髓中CKS1B扩增细胞的百分比和扩增水平显著增加。在该队列患者中,CKS1B在MM中频繁扩增,可能代表与疾病进展相关的基因不稳定。