Normandie University, UNIROUEN, UNICAEN, INSERM1245, MICAH, Avenue de la côte de Nacre, 14033, Caen, France.
Laboratory Hematology, University Hospital Caen, Avenue de la Côte de Nacre, 14033, Caen cedex, France.
J Cancer Res Clin Oncol. 2022 Aug;148(8):2013-2022. doi: 10.1007/s00432-022-04010-4. Epub 2022 Apr 27.
Hairy cell leukemia (HCL) is a rare chronic B cell malignancy, characterized by infiltration of bone marrow, blood and spleen by typical "hairy cells" that bear the BRAFV600E mutation. However, in addition to the intrinsic activation of the MAP kinase pathway as a consequence of the BRAFV600E mutation, the potential participation of other signaling pathways to the pathophysiology of the disease remains unclear as the precise origin of the malignant hairy B cells.
Using mRNA gene expression profiling based on the Nanostring technology and the analysis of 290 genes with crucial roles in B cell lymphomas, we defined a 17 gene expression signature specific for HCL.
Separate analysis of samples from classical and variant forms of hairy cell leukemia showed almost similar mRNA expression profiles apart from overexpression in vHCL of the immune checkpoints CD274 and PDCD1LG2 and underexpression of FAS. Our results point to a post-germinal memory B cell origin and in some samples to the activation of the non-canonical NF-κB pathway.
This study provides a better understanding of the pathogenesis of HCL and describes new and potential targets for treatment approaches and guidance for studies in the molecular mechanisms of HCL.
毛细胞白血病（HCL）是一种罕见的慢性 B 细胞恶性肿瘤，其特征是典型的“绒毛细胞”浸润骨髓、血液和脾脏，这些细胞携带 BRAFV600E 突变。然而，除了 BRAFV600E 突变导致 MAP 激酶途径的固有激活之外，其他信号通路对疾病病理生理学的潜在参与仍不清楚，因为恶性绒毛 B 细胞的精确起源尚不清楚。
我们使用基于 Nanostring 技术的 mRNA 基因表达谱分析和 290 个对 B 细胞淋巴瘤具有关键作用的基因分析，定义了一个特定于 HCL 的 17 个基因表达特征。
对经典和变异形式的毛细胞白血病样本的单独分析表明，除了 vHCL 中免疫检查点 CD274 和 PDCD1LG2 的过度表达以及 FAS 的表达不足外，mRNA 表达谱几乎相似。我们的结果表明，它起源于生发后记忆 B 细胞，并且在一些样本中激活了非经典 NF-κB 途径。
这项研究提供了对 HCL 发病机制的更好理解，并描述了新的和潜在的治疗方法靶点，并为 HCL 的分子机制研究提供了指导。
