Sézary综合征源于严重突变的造血祖细胞。
Sézary syndrome originates from heavily mutated hematopoietic progenitors.
发表日期：2023 Aug 02
作者：
Carly M Harro, Kimberly B Sprenger, Ricardo A Chaurio, John J Powers, Patrick Innamarato, Carmen M Anadon, Yumeng Zhang, Subir Biswas, Gunjan Mandal, Jessica A Mine, Carla Cortina, Mate Z Nagy, Alexandra L Martin, Katelyn F Handley, Gustavo J Borjas, Pei-Ling Chen, Javier Pinilla-Ibarz, Lubomir Sokol, Xiaoqing Yu, Jose R Conejo-Garcia
来源：
Cellular & Molecular Immunology
摘要：
经过对7例Cutaneous T细胞淋巴瘤（CTCL）患者的外周血液中32,619个CD3+CD4+，CD26+/CD7+和29,932个CD3+CD4+，CD26-/CD7-淋巴细胞进行了单细胞RNA/TCR测序，以及26,411个CD3+CD4+，CD26+/CD7+和33,841个CD3+CD4+，CD26-/CD7-淋巴细胞的单细胞ATAC-seq检测，揭示了副丝裂源淋巴瘤（SS）和真菌性肉芽肿（MF）中的肿瘤细胞表现出不同的表型和分化轨迹。与MF相比，副丝裂细胞表现出更窄的TCR复分布并且富集克隆。令人惊讶的是，在多个副丝裂源综合征患者的造血干细胞中鉴定到了≥200个突变。关键致癌基因中的突变也存在于外周副丝裂细胞中，这些细胞还显示出最近胸腺出膜的特征。综合我们的数据表明，CTCL起源于在胸腺获得TCR的突变淋巴细胞祖细胞，而在外周完成了其恶性转化。©2023年美国血液学协会版权所有。
The pathogenesis of Cutaneous T cell lymphoma (CTCL) remains unclear. Using single-cell RNA/TCR sequencing of 32,619 CD3+CD4+, CD26+/CD7+ and 29,932 CD3+CD4+, CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-seq of 26,411 CD3+CD4+, CD26+/CD7+ and 33,841 CD3+CD4+, CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome (SS) and Mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment. Surprisingly, we identified ≥200 mutations in hematopoietic stem cells from multiple Sézary syndrome patients. Mutations in key oncogenes were also present in peripheral Sézary cells, which also showed the hallmarks of recent thymic egression. Together our data suggest that CTCL arises from mutated lymphocyte progenitors that acquire TCRs in the thymus, which complete their malignant transformation in the periphery.Copyright © 2023 American Society of Hematology.