Detection of Chromosomal Aberrations in CLL and Correlation with Clinical Staging.

Abstract

Chromosome abnormalities detected in CLL are important markers for determination of treatment approaches. This study was aimed to evaluate usefulness of FISH panels for testing chromosome aberrations in CLL and to correlate the aberrations with clinical staging of disease and responses to chlorombucil therapy. Cytogenetics and FISH analyses from bone marrow samples of 67 CLL patients were performed according to standard unstimulated short term culture methods. CLL specific FISH panel included probes for 11q22.3 (LSIATM), CEP12, 13q14 (LSID13S19 and LSID13S25), 17p13.1 (LSIp53). FISH analysis was performed in all samples. The most commonly seen abnormality was 13q14 deletion followed by deletions of ATM, p53 and trisomy12. Of 19 cases with 13q14 deletion, 11 had only this abnormality whereas the others had trisomy12, p53 and ATM loci deletions (multiple abnormalities). Of 11 cases with single abnormality, 8 were at stage A, 3 was at stage C and all patients achieved benefits from chlorombucil therapy except one patient. Failed therapy response was seen in 9 patients with multiple abnormalities and the disease was at stage C (4 cases) and B (5 cases). Patients showing p53 and ATM deletions related with poor prognosis had progressive disease and no benefit could be achieved from chlorombucil therapy. Of 6 cases with trisomy 12, 4 were at early stage and response to the therapy was good but in two cases at later stage, therapy benefit could be achieved in one while no benefit was seen in the other one. The results showed that FISH analysis is more informative than karyotype analysis in CLL. Detection of p53 and ATM loci deletions is an important marker for administration of second level therapy.