A High Number of Losses in 13q14 Chromosome Is Associated with a Worse Outcome and Biological Differences in Patients with B Chronic Lymphoid Leukemia.

Abstract Background: Cytogenetic abnormalities in B chronic lymphoid leukemia (B-CLL) define groups of patients with different prognosis. Thus, patients with B-CLL and 13q14 deletion display a favourable outcome. However, whether the percentage of cells showing 13q-, as it has been demonstrated in other genetic aberrations such as loss of P53, could influence the prognosis or the biological characteristics of the disease remains unknown. Aim: To analyze the clinical and biological characteristics of B-CLL displaying, at diagnosis, loss of 13q as the sole cytogenetic aberration. Patients, material and methods: A total of 350 patients diagnosed of B-CLL were included. All the clinical data as well as FISH information (13q14, 12, 11q21, 14q32 and 17p13 probes) and molecular studies were carried out. In addition, a gene expression profile from a microarray-based analysis was also performed. Results: One hundred and sixty-two patients (46.3 %) had 13q14 deletion. In 109 out of the 350 cases (31.1 %) loss of 13q was the sole cytogenetic aberration at diagnosis. Interestingly, in the subgroup of patients with ³ 80 % of cells with loss of 13q (18 cases, 15.5%), the OS was 143 months (95 % CI: 104 m-154 m), while in the group with < 80 % of losses in 13q, the OS has not been reached (95 % CI: 175 m-253 m). In the multivariate analysis for OS in patients with 13q-, the variables included in the final model were the percentage of losses of 13q14 (P = 0.001) and the presence of B symptoms (P = 0.007). Regarding the time to the first therapy (TFT), in the group with more than 80 % of losses in 13q the median TFT was 134 months while in the group of patients with < 80 % of losses it was 38 months (P = 0.05). In the multivariate analysis for TFT in patients with 13q- the variables selected were unmutated status of IgVH (P = 0.001) and a high level of b2microglobulin (P = 0.003). In addition, the gene expression profile showed that patients with a high number of losses in 13q14 had a high proliferation rate, downregulation of genes apoptosis-related, and deregulation of genes related to mitochondrial functions compared to B-CLL patients with low numbers of 13q- cells. Conclusion: B-CLL patients with a high number of losses in 13q14 as the sole cytogenetic aberration display different clinical and biological features: short OS and TFT as well as more proliferation and less apoptosis. Therefore, a quantification of the number of cells showing a genetic abnormality should be included in the study of the prognostic factors of B-CLL.