Receptores estereotipados en pacientes con leucemia linfocítica crónica. Frecuencia y distribución en diferentes países de Latinoamérica

The IGHV (immunoglobulin heavy chain variable region) gene mutational status is considered an important prognostic factor in chronic lymphocytic leukemia (CLL). We have evaluated the presence of IGHV mutational status, gene usage and stereotyped B-cell receptors (BCRSs) in CLL patients from a multicenter study developed in the context of the Latin American Group of CLL (LAG-CLL). Our cohort included 431 unselected CLL patients from Argentina (253), Uruguay (99) and Venezuela (79). Analysis of data showed over-representation of mutated cases. Concerning IGHV family usage, VH3>VH4>VH1 distribution was found in Argentina, while VH3>VH1>VH4 was observed in the other countries. The most frequently used IGHV genes were IGHV1-69, IGHV3-23 and IGHV4-34. IGHV3-21 was present in 10% of Venezuelan patients but showed lower frequencies in the Uruguayan (2%) cohort and intermediate frequency in the Argentinean series (6.7%). BCRSs were observed in 15.2% of total cases. Two novel potential subsets were detected. IGHV3-21 gene was always included in the heterogeneous group in Venezuelan cohorts. Argentinean series exhibit over-representation of cluster #2 (3.13%), while Uruguay showed the highest frequency of cluster #4 (4.04%). Venezuelan CLL patients showed very low percentages of major clusters (5.1%). These results are the first integrated IGHV analysis from Latin American countries. They showed interesting differences, reflecting variations in the genetic background and/or differences in environmental factors operating in CLL pathogenesis in this particular geographic area.