Abstract
A specific role for increased level of expression of CKS1B, as a consequence of chromosome 1q21 copy number gain, has been postulated as both pathogenic, as well as a powerful clinical prognostic factor in multiple myeloma (MM). The purpose of this study is to determine the clinical associations and prognostic impact of copy number gain at chromosome 1q21 (with a bacteria artificial chromosome clone containing CKS1B) and CKS1B gene level of expression in MM. We studied the chromosome region 1q21 for copy number change in a cohort of myeloma patients treated by high-dose therapy with stem-cell rescue (HDT) (n=159). A separate cohort of patients, treated by HDT was studied for CKS1B messenger RNA expression by gene expression profiling (n=67). 1q21 gain was then correlated with clinical parameters and survival. Gain of 1q21 copy number was detected in about a third of MM and was associated with more proliferative disease and poor-risk cytogenetic categories such as t(4;14), and chromosome 13 deletion. Both 1q21 gain and increase gene expression level were significantly associated with reduced survival. However, neither is an independent prognostic marker in MM on multivariate Cox proportional hazard analysis.
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Acknowledgements
RF is a Clinical Investigator of the Damon Runyon Cancer Research Fund. This work was supported by the International Waldenström Macroglobulinemia Foundation, and Grants R01 CA83724-01, SPORE P50 CA100707-01, the Donaldson Charitable Trust fund and P01 CA62242 from the National Cancer Institute, and the Fund to Cure Myeloma. WJC is funded by an International Fellowship from the Agency for Science, Technology and Research, Singapore (A*STAR).
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Fonseca, R., Van Wier, S., Chng, W. et al. Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma. Leukemia 20, 2034–2040 (2006). https://doi.org/10.1038/sj.leu.2404403
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DOI: https://doi.org/10.1038/sj.leu.2404403
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