Structural alterations in chronic lymphocytic leukaemia. Cytogenetic and FISH analysis.

In this study, we described cytogenetics and fluorescence in situ hybridization (FISH) analysis performed in chronic lymphocytic leukaemia (CLL) patients with structural alterations. Results were correlated with clinical characteristics. A total of 38 CLL patients: 16 cases with complex and 22 with simple karyotypes were studied. For comparison of clinical parameters, a control group of 78 CLL patients with normal karyotype and without FISH genomic alterations were also evaluated. We found 38 structural abnormalities not previously described in the literature, 28 (74%) of them were translocations. In cases with complex karyotypes, chromosomes 6, 8 and 13 were the most frequently involved in new alterations (nine each), followed by chromosomes 12, 14 and 15 (six each). Chromosome 8p was particularly involved in losses, being 8p21-pter the commonest region of overlap. Cases with simple karyotypes, showed del(6q) as the most frequent alteration (39%). Del(9)(q11) was recurrent in our series. Analysis of clinical parameters showed significant differences in white blood count (p = 0.005) and platelet count (p = 0.015) between patients with structural alterations and the control group. In addition, patients with structural alterations had a significantly shorter time to first treatment (TFT) (29 months) than the control group (69 months) (p = 0.037). Cases with complex karyotypes had a lower proportion of patients in Rai 0 clinical stage (15.4% vs 75%) (p = 0.005) and higher ß2 microglobulin levels (3.3 vs 2.5 µg/mL) (p = 0.037) than those with simple karyotypes. Furthermore, a shorter TFT (13 months) and overall survival (56 months) in the complex karyotypes group compared with controls (69 and 144 months, respectively) (p = 0.015 and p = 0.005, respectively) were also found. Our results support the importance of cytogenetic analysis for clinical outcome in CLL and suggest that the diversity of genomic alterations is much greater than previously appreciated.

Genetic abnormalities and clinical outcome in chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the elderly population. Under conventional cytogenetic (CC) analysis, approximately 50% of CLL cases show clonal aberrations. Using fluorescent in situ hybridization (FISH), the percentage of patients with abnormalities rises to almost 80%, the most frequent being 13q14, ATM, and TP53 deletions and trisomy 12. The aim of this study was to establish the incidence of genetic changes in B-CLL patients using CC and FISH and to evaluate the prognostic implications. Of the 65 patients analyzed, genetic aberrations were found in 36.7% with CC and in 68.4% with FISH. The frequencies of abnormalities were as follows: 13q deletion, 42.1%; trisomy 12, 19.2%; ATM deletion, 17.5%; and TP53 deletion, 8.7%. Significant differences were observed when the overall survival was correlated with Rai stage (P = 0.000). FISH abnormalities were correlated with age, sex, morphology, white blood cell count, CD38 expression, Rai stage, disease status, and survival. Significant differences were obtained with age (P = 0.05) and disease status (P = 0.01). Deletion of 13q was the most frequent abnormality (36.6%) among old patients (> or =60); trisomy 12 was the most frequent (31.3%) in younger patients (<60). Half of the patients with stable disease showed 13q deletion, and the most frequent abnormality in patients with progressive disease was ATM deletion (22.2%).