PMID- 28249016
OWN - NLM
STAT- MEDLINE
DCOM- 20170817
LR  - 20210103
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 3
DP  - 2017
TI  - HLA specificities are associated with prognosis in IGHV-mutated CLL-like 
      high-count monoclonal B cell lymphocytosis.
PG  - e0172978
LID - 10.1371/journal.pone.0172978 [doi]
LID - e0172978
AB  - 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.
FAU - Garcia-Alvarez, Maria
AU  - Garcia-Alvarez M
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Alcoceba, Miguel
AU  - Alcoceba M
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
AD  - CIBERONC, Madrid, Spain.
FAU - Lopez-Parra, Miriam
AU  - Lopez-Parra M
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Puig, Noemi
AU  - Puig N
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Anton, Alicia
AU  - Anton A
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Balanzategui, Ana
AU  - Balanzategui A
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Prieto-Conde, Isabel
AU  - Prieto-Conde I
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Jimenez, Cristina
AU  - Jimenez C
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Sarasquete, Maria E
AU  - Sarasquete ME
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Chillon, M Carmen
AU  - Chillon MC
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
AD  - CIBERONC, Madrid, Spain.
FAU - Gutierrez, Maria Laura
AU  - Gutierrez ML
AD  - Cytometry Service-NUCLEUS, Department of Medicine, Cancer Research Center 
      (IBMCC-CSIC/USAL) and IBSAL (University of Salamanca), Salamanca, Spain.
FAU - Corral, Rocio
AU  - Corral R
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Alonso, Jose Maria
AU  - Alonso JM
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
FAU - Queizan, Jose Antonio
AU  - Queizan JA
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
FAU - Vidan, Julia
AU  - Vidan J
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
FAU - Pardal, Emilia
AU  - Pardal E
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
FAU - Penarrubia, Maria Jesus
AU  - Penarrubia MJ
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
FAU - Bastida, Jose M
AU  - Bastida JM
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
FAU - Garcia-Sanz, Ramon
AU  - Garcia-Sanz R
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
FAU - Marin, Luis
AU  - Marin L
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
AD  - CIBERONC, Madrid, Spain.
FAU - Gonzalez, Marcos
AU  - Gonzalez M
AD  - Department of Hematology, University Hospital of Salamanca (HUS-IBSAL), 
      Salamanca, Spain.
AD  - Cooperative Working Group on Lymphomas and Lymphoproliferative Disorders of the 
      Castilla y Leon Society of Hematology and Hemotherapy (SCLHH), Castilla y Leon, 
      Spain.
AD  - CIBERONC, Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20170301
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B-Lymphocytes/pathology
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Female
MH  - *Genes, Immunoglobulin Heavy Chain
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
MH  - Lymphocyte Count
MH  - Lymphocytosis/blood/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Prognosis
PMC - PMC5332061
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/03/02 06:00
MHDA- 2017/08/18 06:00
PMCR- 2017/03/01
CRDT- 2017/03/02 06:00
PHST- 2016/09/13 00:00 [received]
PHST- 2017/02/12 00:00 [accepted]
PHST- 2017/03/02 06:00 [entrez]
PHST- 2017/03/02 06:00 [pubmed]
PHST- 2017/08/18 06:00 [medline]
PHST- 2017/03/01 00:00 [pmc-release]
AID - PONE-D-16-36806 [pii]
AID - 10.1371/journal.pone.0172978 [doi]
PST - epublish
SO  - PLoS One. 2017 Mar 1;12(3):e0172978. doi: 10.1371/journal.pone.0172978. 
      eCollection 2017.