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- Kaderi, Mohd Arifin, et al.
(författare)
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Lack of association between the MDM2 promoter polymorphism SNP309 and clinical outcome in chronic lymphocytic leukemia
- 2010
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 34:3, s. 335-339
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Tidskriftsartikel (refereegranskat)abstract
- The 309T>G polymorphism in the promoter region of the MDM2gene, known as SNP309, has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. To investigate this further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated the results with established CLL prognostic factors, time to treatment and overall survival. In this Swedish cohort, no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment. Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet stage, IGHV mutational status and recurrent genomic aberrations. In summary, this study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL.
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| 2. |
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| 3. |
- Sevov, Marie, et al.
(författare)
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Longitudinal study of RNA-based prognostic markers in chronic lymphocytic leukemia reveals LPL as the most stable
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Several genes display differential expression in prognostic subsets in chronic lymphocytic leukemia (CLL), including LPL, TCL1, ZAP70 and MCL1. CLL patients commonly have an indolent course with low stage disease and long survival, and in this study we aimed to investigate the stability of RNA-based prognostic markers in such an indolent cohort over time. mRNA expression of LPL, TCL1, ZAP70 and MCL1 was measured in sequential unsorted samples obtained from 96 CLL patients at both diagnosis and a median follow-up of seven years. LPL was the only RNA-based marker that did not demonstrate any significant changes in expression in diagnostic vs. follow-up samples. Furthermore, an 82% concordance between both time-points was observed when grouping cases based on high or low expression. LPL expression was not affected by treatment and in addition, LPL expression in follow-up samples could predict overall survival. In contrast, TCL1 expression was found to increase at follow-up, especially in cases displaying low expression at diagnosis. As TCL1 promotes cell survival this increase could possibly be of importance for progression of the disease. Both ZAP70 and MCL1 mRNA expression were found to vary significantly during the disease course. In summary, using unsorted CLL samples, we have demonstrated that LPL is superior to other RNA-based markers based on stability over time. These findings fully endorse the use of LPL analysis at any time point of the disease.
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