Stella Flavia, Pedrazzini Estela, Baialardo Edgardo, Fantl Dorotea Beatriz, Schutz Natalia, Slavutsky Irma
Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina; Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA), Argentina.
Blood Cells Mol Dis. 2014 Sep;53(3):110-7. doi: 10.1016/j.bcmd.2014.05.006. Epub 2014 Jun 25.
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 β2 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.
在本研究中，我们检测了114例患者诊断时CKS1B基因的表达和拷贝数：83例多发性骨髓瘤（MM）患者和31例意义未明的单克隆丙种球蛋白病（MGUS）患者。结果与细胞遗传学、荧光原位杂交（FISH）及临床特征相关。检测发现，与MGUS病例相比，MM患者的CKS1B mRNA水平有显著差异（p<0.048）。在MM中，核型异常患者的1q21（CKS1B）拷贝数增加频率显著高于核型正常患者（p=0.021）。整体分析显示CKS1B表达与1q21拷贝数之间呈正相关（p<0.0001）。未发现CKS1B mRNA表达与临床参数之间存在关联。然而，观察到1q21拷贝数增加的病例中β2微球蛋白水平显著高于未增加的病例（p=0.0094）。与1q21区域正常的病例相比，1q21拷贝数增加的病例总生存期更短（p=0.0082）。我们的结果表明CKS1B在MGUS进展为MM的多步骤过程中发挥作用，且表明CKS1B拷贝数增加比其过表达具有更显著的预后价值。这种对生存的不利影响可能反映了与1号染色体q臂改变相关的基因不稳定性，导致疾病行为更具侵袭性。
