Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León, European Commission, García-Alvarez, María, Alcoceba, Miguel, López-Parra, Miriam, Puig, Noemi, Antón, Alicia, Balanzategui, Ana, Prieto-Conde, Isabel, Jiménez, Cristina, Sarasquete, María Eugenia, Chillón, M. del Carmen, Gutiérrez, María Laura, Corral, Rocío, Alonso, José M., Queizán, José-Antonio, Vidán, Julia, Pardal, Emilia, Peñarrubia, María J., Bastida, José María, García-Sanz, Ramón, Marín, Luis, González, Marcos, Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León, European Commission, García-Alvarez, María, Alcoceba, Miguel, López-Parra, Miriam, Puig, Noemi, Antón, Alicia, Balanzategui, Ana, Prieto-Conde, Isabel, Jiménez, Cristina, Sarasquete, María Eugenia, Chillón, M. del Carmen, Gutiérrez, María Laura, Corral, Rocío, Alonso, José M., Queizán, José-Antonio, Vidán, Julia, Pardal, Emilia, Peñarrubia, María J., Bastida, José María, García-Sanz, Ramón, Marín, Luis, and González, Marcos
[Introduction]: Molecular alterations leading progression of asymptomatic CLL-like high-count monoclonal B lymphocytosis (hiMBL) to chronic lymphocytic leukemia (CLL) remain poorly understood. Recently, genome-wide association studies have found 6p21.3, where the human leukocyte antigen (HLA) system is coded, to be a susceptibility risk region for CLL. Previous studies have produced discrepant results regarding the association between HLA and CLL development and outcome, but no studies have been performed on hiMBL. [Aims]: We evaluated the role of HLA class I (-A, -B and -C) and class II (-DRB1 and -DQB1) in hiMBL/CLL susceptibility, hiMBL progression to CLL, and treatment requirement in a large series of 263 patients diagnosed in our center with hiMBL (n = 156) or Binet A CLL (n = 107). [Results]: No consistent association between HLA specificities and hiMBL or CLL susceptibility was found. With a median follow-up of 7.7 years, 48/156 hiMBLs (33%) evolved to asymptomatic CLLs, while 16 hiMBLs (10%) and 44 CLLs (41%) required treatment. No HLA specificities were found to be significantly associated with hiMBL progression or treatment in the whole cohort. However, within antigen-experienced immunoglobulin heavy-chain (IGHV)-mutated hiMBLs, which represents the highest proportion of hiMBL cases (81%), the presence of HLA-DQB1∗03 showed a trend to a higher risk of progression to CLL (60% vs. 26%, P = 0.062). Moreover, HLA-DQB1∗02 specificity was associated with a lesser requirement for 15-year treatment (10% vs. 36%, P = 0.012). [Conclusion]: In conclusion, our results suggest a role for HLA in IGHV-mutated hiMBL prognosis, and are consistent with the growing evidence of the influence of 6p21 on predisposition to CLL. Larger non-biased series are required to enable definitive conclusions to be drawn.