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2 results on '"María Jesús Peñarrubia"'

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

Author

María García-Álvarez, Miguel Alcoceba, Miriam López-Parra, Noemí Puig, Alicia Antón, Ana Balanzategui, Isabel Prieto-Conde, Cristina Jiménez, María E Sarasquete, M Carmen Chillón, María Laura Gutiérrez, Rocío Corral, José María Alonso, José Antonio Queizán, Julia Vidán, Emilia Pardal, María Jesús Peñarrubia, José M Bastida, Ramón García-Sanz, Luis Marín, and Marcos González

Subjects
Medicine, Science
Abstract

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.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).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).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.

Published
2017
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2. HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis

Author

Alicia Antón, Miguel Alcoceba, Julia Vidán, Cristina Jimenez, Ana Balanzategui, Ramón García-Sanz, María Jesús Peñarrubia, María García-Álvarez, María Eugenia Sarasquete, Noemi Puig, Luis Marín, Isabel Prieto-Conde, M. Carmen Chillón, Marcos González, José María Bastida, Rocío Corral, Emilia Pardal, María Laura Gutiérrez, José Antonio Queizán, Miriam López-Parra, José María Quiroga Alonso, Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León, and European Commission

Subjects
Male, 0301 basic medicine, B Cells, Lymphocytosis, Cell Transplantation, Chronic lymphocytic leukemia, lcsh:Medicine, Hematologic Cancers and Related Disorders, White Blood Cells, Mathematical and Statistical Techniques, 0302 clinical medicine, Animal Cells, immune system diseases, hemic and lymphatic diseases, Medicine and Health Sciences, Blood and Lymphatic System Procedures, Lymphocytes, lcsh:Science, Chronic Lymphoblastic Leukemia, Aged, 80 and over, B-Lymphocytes, Multidisciplinary, biology, Hematology, Genomics, Middle Aged, Prognosis, Oncology, Physical Sciences, Monoclonal, Lymphoblastic Leukemia, Monoclonal B-cell lymphocytosis, Chromosomes, Human, Pair 6, Female, Cellular Types, medicine.symptom, Antibody, IGHV@, Statistics (Mathematics), Research Article, Adult, Immune Cells, Genes, Immunoglobulin Heavy Chain, Immunology, Cell Enumeration Techniques, Surgical and Invasive Medical Procedures, Human leukocyte antigen, Research and Analysis Methods, Asymptomatic, 03 medical and health sciences, Diagnostic Medicine, Leukemias, Genome-Wide Association Studies, Genetics, medicine, Humans, Lymphocyte Count, Statistical Methods, Antibody-Producing Cells, Aged, Transplantation, Blood Cells, business.industry, Histocompatibility Antigens Class I, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, Computational Biology, Human Genetics, Cell Biology, Genome Analysis, medicine.disease, 030104 developmental biology, Multivariate Analysis, Mutation, biology.protein, lcsh:Q, business, Mathematics, Stem Cell Transplantation, 030215 immunology
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., This work was supported in part by Grants from the Hematology and Hemotherapy Society of Castilla-León (#1 FUCALHH-2010), and the Instituto de Salud Carlos III (ISCIII), award numbers (#2) RTICC-RD12/0036/0069, (#3) CIBERONC CB16/12/00233, and (#4) Innocampus; CEI-2010-1-0010. All ISCIII funding was co- sponsored by the European Union FEDER program.

Published
2017

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