HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis.

HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis.

PLoS One. 2017;12(3):e0172978

Authors: García-Álvarez M, Alcoceba M, López-Parra M, Puig N, Antón A, Balanzategui A, Prieto-Conde I, Jiménez C, Sarasquete ME, Chillón MC, Gutiérrez ML, Corral R, Alonso JM, Queizán JA, Vidán J, Pardal E, Peñarrubia MJ, Bastida JM, García-Sanz R, Marín L, González M

Abstract
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.

PMID: 28249016 [PubMed - in process]

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