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

AuthorsGarcía-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, Jose M.; Queizán, José-Antonio; Vidán, Julia; Pardal, Emilia; Peñarrubia, María J.; Bastida, J. M.; García-Sanz, Ramón; Marín, Luis; González, Marcos
Issue Date2017
PublisherPublic Library of Science
CitationPLoS ONE 12(3): e0172978 (2017)
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.
Publisher version (URL)https://doi.org/10.1371/journal.pone.0172978
Identifiersdoi: 10.1371/journal.pone.0172978
e-issn: 1932-6203
Appears in Collections:(IBMCC) Artículos
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