Expression of cyclin D1 demonstrated by immunohistochemistry is seen in 95% of mantle cell lymphomas and in other lymphoproliferative diseases including 10% of chronic lymphocytic leukemias (CLL). This study analyzed the impact of cyclin D1 positivity on time to treatment (TTT) and overall survival (OS) measured by RT PCR in newly diagnosed CLL patients and correlation with reported prognostic factors.
Level of cyclin D1 (quantitative real-time RT-PCR with a specific TaqMan flurescent hybridization probe) mRNA expression was analysed in 72 samples (57 peripheral blood and 15 bone marrow) from patients with newly diagnosed CLL. Cyclin D1 expression (cut-off according to ROC curve >3 over the threshold expression in healthy donors) was reported as positive. Fisher's exact test was used to analyze the relationship of cyclin D1 positivity and prognostic factors: del17p, del11q, unmutated IgVH, trisomy 12, ZAP 70 and CD38 positivity, elevated B2microglobulin, elevated LDH and lymphocyte doubling time (LDT) <6 months. The comparison of time to treatment (TTT) and prognostic factors with cyclin D1 positivity was calculated via Spearman correlation coefficient. Survival curves were calculated by Kaplan-Meier survival analysis and comparison between subgroups was performed by the log-rank test.
Cyclin D1 was positive in 29 (40%) CLL patients. Although cyclin D1 was not statistically significant for TTT (P=0,145), a trend was observed, suggesting a negative prognostic impact of cyclin D1 overexpression in CLL. Following variables correlated significantly with TTT: del17p (P=0.037), del11q (P=0.003), unmutated IgVH (P=0.004), trisomy 12(P=0.024), positive CD38 (P=0.014), elevated B2microglobulin (P<0.001), elevated LDH (P<0.001) and LDT <6 months (P<0.001). Del 17p, del 11q, trisomy 12 and elevated B2microglobulin were independent factors for TTT in the multivariate analysis. None of these factors were significant for overall survival due to the short follow-up.
Cyclin D1 measured by RT-PCR from peripheral blood or bone marrow has no statistically singificant impact on TTT or OS, though a trend pointing to cyclin D1 overexpression in CLL as a negative prognostic marker can be suggested. This data should be confirmed on a larger cohort of patients with a longer follow-up.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.