Cell Cycle Genes Coexpression in Multiple Myeloma and Plasma Cell Leukemia
| Authors | |
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| Year of publication | 2013 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | The regulation of cell cycle is dynamic and is determined not by the absolute level of any regulator, but by the aggregate balance between positive/negative cell-cycle regulators and the interplay among them. The objective of study was to describe coexpression correlations of cell cycle regulatory genes in MM and PCL. Chosen genes, responsible for G1-to-S cell-cycle progression, were divided into 2 groups based on their regulatory role: activators and blockers. Comparison of gene expression (qRT-PCR) in MM and PCL revealed up-regulation of CDKN2A (2.7-fold change, p=0.045) and CCND1 (7.9-fold change, p=0.005) in PCL samples. In PCL cohort, CCND1 and CDK6 expression lost correlation with blocker genes and CDKN1B expression lost correlation with activator genes. For CDKN2A and CDKN1A blocker genes loss of correlation with some activators were associated with significant increasing of correlation with other ones. Such reaction can be explained by compensation mechanisms. Univariate Cox proportional hazards survival model with one explanatory variable showed prognostic impact for CDKN2A (HR 1.022 [HR95%CI: 1.004; 1.040]; p=0.016) and CCND3 (HR 1.489 [HR95%CI: 1.112; 1.993]; p=0.008) in MM cohort. Thus, our data highlight changes in correlations between cell cycle blockers and activators during MM to PCL progression. Despite compensation mechanisms activation (CDKN2A, CDKN1A) whole regulatory complex seems to be imbalanced (CCND1, CDK6, CDKN1B), which can be explained by severe cell cycle dysregulation during progression to PCL. |
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