CONICET | Buscador de Institutos y Recursos Humanos

Background: Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. The mutational status of the immunoglobulin heavy chain variable (IGHV) region represent one of the best prognostic markers and defines two disease subgroups: mutated (M-CLL) and unmutated (UM-CLL), with different clinical course. Materials and Methods: IGHV-D-J gene rearrangements and mutational status were analyzed in 73 Argentinean CLL patients, 22 previously treated, by reverse transcriptase-polymerase chain reaction and bi-directional sequencing. Results were compared with those reported in other geographic regions. FISH analysis was also performed. Results: Forty three (58.9%) cases were M-CLL, and 30 (41.1%) were UM-CLL. Deletion 13q14 as a single alteration was more frequently observed in M-CLL (48%) than in UM-CLL (24%). In the M-group, the proportion of cases with deletion 13q14 was significantly higher than those with +12 (12%) and, deletions 17p and 11q (11.7%) (p=0.003). The most frequently used IGHV families were IGHV3>IGHV1>IGHV4, different to those observed in Asian, Brazilian and Uruguayan series. IGHV3-23 gene (10.8%) was the most commonly used, followed by IGHV1-69 (9.5%), IGHV4-59 and IGHV2-5 (6.8% each), IGHV3-21 and IGHV3-30 (5.4% each). IGHV4-34 showed the lowest frequency (2.7%) in our cohort compared to published data, while IGHV4-59, IGHV3-72 and IGHV2-5 were overexpressed in our series. Stereotyped HCDR3 were found in 9.5% patients. Conclusions: Our results showed that Argentinean CLL patients display an IGHV gene usage which resembles that observed in Western countries and exhibit interesting similarities and differences with respect to published series from other Latin American populations, reflecting variations in the genetic background.