title: HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Álvarez
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.|Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.|CIBERONC, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcoceba
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: López-Parra
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Puig
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Antón
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Prieto-Conde
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jiménez
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.|CIBERONC, Madrid, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Chillón
authors.affiliation: Cytometry Service-NUCLEUS, Department of Medicine, Cancer Research Center (IBMCC-CSIC/USAL) and IBSAL (University of Salamanca), Salamanca, Spain.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Gutiérrez
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Corral
authors.affiliation: Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Alonso
authors.affiliation: Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Queizán
authors.affiliation: Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Vidán
authors.affiliation: Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.
authors.forename: Emilia
authors.initials: E
authors.lastname: Pardal
authors.affiliation: Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Peñarrubia
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Bastida
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.|Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.|CIBERONC, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Marín
authors.affiliation: Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), Salamanca, Spain.|Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the Castilla y León Society of Hematology and Hemotherapy (SCLHH), Castilla y León, Spain.|CIBERONC, Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis
chemical_list: D015395:Histocompatibility Antigens Class I