Università della Svizzera Italiana, Institute of Oncology Research, Bellinzona, Switzerland.
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Blood Adv. 2019 Feb 12;3(3):384-396. doi: 10.1182/bloodadvances.2018024059.
Classic hairy cell leukemia (HCL) is a tumor of mature clonal B cells with unique genetic, morphologic, and phenotypic features. DNA methylation profiling has provided a new tier of investigation to gain insight into the origin and behavior of B-cell malignancies; however, the methylation profile of HCL has not been specifically investigated. DNA methylation profiling was analyzed with the Infinium HumanMethylation27 array in 41 mature B-cell tumors, including 11 HCL, 7 splenic marginal zone lymphomas (SMZLs), and chronic lymphocytic leukemia with an unmutated (n = 7) or mutated (n = 6) immunoglobulin gene heavy chain variable (IGHV) region or using IGHV3-21 (n = 10). Methylation profiles of nontumor B-cell subsets and gene expression profiling data were obtained from public databases. HCL had a methylation signature distinct from each B-cell tumor entity, including the closest entity, SMZL. Comparison with normal B-cell subsets revealed the strongest similarity with postgerminal center (GC) B cells and a clear separation from pre-GC and GC cellular programs. Comparison of the integrated analysis with post-GC B cells revealed significant hypomethylation and overexpression of BCR-TLR-NF-κB and BRAF-MAPK signaling pathways and cell adhesion, as well as hypermethylation and underexpression of cell-differentiation markers and methylated genes in cancer, suggesting regulation of the transformed hairy cells through specific components of the B-cell receptor and the BRAF signaling pathways. Our data identify a specific methylation profile of HCL, which may help to distinguish it from other mature B-cell tumors.
经典型毛细胞白血病（HCL）是一种成熟克隆 B 细胞肿瘤，具有独特的遗传、形态和表型特征。DNA 甲基化谱分析为深入了解 B 细胞恶性肿瘤的起源和行为提供了一个新的研究层次；然而，HCL 的甲基化谱尚未得到专门研究。我们用 Infinium HumanMethylation27 阵列分析了 41 种成熟 B 细胞肿瘤，包括 11 例 HCL、7 例脾边缘区淋巴瘤（SMZL）、7 例未突变（n = 7）或突变（n = 6）免疫球蛋白基因重链可变区（IGHV）的慢性淋巴细胞白血病，或使用 IGHV3-21（n = 10）。从公共数据库获得了非肿瘤 B 细胞亚群的甲基化谱和基因表达谱数据。HCL 的甲基化特征与每种 B 细胞肿瘤实体均不同，包括最接近的实体 SMZL。与正常 B 细胞亚群的比较显示与生发中心后（GC）B 细胞的相似性最强，与 GC 前和 GC 细胞程序明显分离。与 GC 后 B 细胞的综合分析比较表明，BCR-TLR-NF-κB 和 BRAF-MAPK 信号通路以及细胞黏附的过度甲基化和过表达，以及细胞分化标记物和甲基化基因的低甲基化和低表达，表明通过 B 细胞受体和 BRAF 信号通路的特定成分调节转化的毛细胞。我们的数据确定了 HCL 的特定甲基化谱，这可能有助于将其与其他成熟 B 细胞肿瘤区分开来。
