García-Álvarez María, Alcoceba Miguel, López-Parra Miriam, Puig Noemí, Antón Alicia, Balanzategui Ana, Prieto-Conde Isabel, Jiménez Cristina, Sarasquete María E, Chillón M Carmen, Gutiérrez María Laura, Corral Rocío, Alonso José María, Queizán José Antonio, Vidán Julia, Pardal Emilia, Peñarrubia María Jesús, Bastida José M, García-Sanz Ramón, Marín Luis, González Marcos
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.
PLoS One. 2017 Mar 1;12(3):e0172978. doi: 10.1371/journal.pone.0172978. eCollection 2017.
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-DQB103 showed a trend to a higher risk of progression to CLL (60% vs. 26%, P = 0.062). Moreover, HLA-DQB102 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.
导致无症状性慢性淋巴细胞白血病样高计数单克隆B淋巴细胞增多症（hiMBL）进展为慢性淋巴细胞白血病（CLL）的分子改变仍知之甚少。最近，全基因组关联研究发现，编码人类白细胞抗原（HLA）系统的6p21.3是CLL的一个易感风险区域。先前的研究关于HLA与CLL发生及预后之间的关联得出了不一致的结果，但尚未有针对hiMBL的研究。
我们评估了HLA I类（-A、-B和-C）和II类（-DRB1和-DQB1）在263例在我们中心诊断为hiMBL（n = 156）或Binet A期CLL（n = 107）的大量患者中的hiMBL/CLL易感性、hiMBL进展为CLL以及治疗需求方面的作用。
未发现HLA特异性与hiMBL或CLL易感性之间存在一致的关联。中位随访7.7年，48/156例hiMBL（33%）进展为无症状CLL，而16例hiMBL（10%）和44例CLL（41%）需要治疗。在整个队列中，未发现HLA特异性与hiMBL进展或治疗有显著关联。然而，在抗原经历的免疫球蛋白重链（IGHV）突变的hiMBL中（占hiMBL病例的比例最高，为81%），HLA-DQB103的存在显示出进展为CLL的风险有升高趋势（60%对26%，P = 0.062）。此外，HLA-DQB102特异性与15年治疗需求较低相关（10%对36%，P = 0.012）。
总之，我们的结果表明HLA在IGHV突变的hiMBL预后中起作用，并且与越来越多的关于6p21对CLL易感性影响的证据一致。需要更大规模的无偏倚队列研究以得出确定性结论。
