Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Hematology, Zhejiang University, Hangzhou, China.
Leuk Lymphoma. 2023 Oct;64(10):1681-1688. doi: 10.1080/10428194.2023.2232493. Epub 2023 Jul 10.
The pathogenesis of donor cell leukemia (DCL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear and likely multifactorial. Leukemic transformation of healthy donor HSCs in recipient's bone marrow microenvironment provides a useful model for investigating the mechanisms involved in leukemogenesis. Here, we report a rare case of late-onset DCL developing in a recipient. Whole-genome sequencing indicates that donor-derived cells harboring clonal hematopoiesis of indeterminate potential (CHIP)-associated genetic alterations expand and eventually transform to full-blown AML acquisition of additional somatic mutations within the recipient's bone marrow microenvironment. The 10× single-cell RNA sequencing reveals the abundance of GMP-like cells with a specific transcriptional signature in DCL. Moreover, impaired immune surveillance, including dysfunction of cytotoxic T lymphocytes (CTLs) and decreased number of canonical NK cells, is discovered in DCL. Our data add valuable information to the current understanding of the mechanisms of DCL.
供者细胞白血病（DCL）是异基因造血干细胞移植（allo-HSCT）后一种发病机制尚不清楚且可能为多因素的疾病。在受者骨髓微环境中，健康供者造血干细胞的白血病转化为研究白血病发生机制提供了一个有用的模型。在这里，我们报告了一例罕见的迟发性 DCL 发生于受者的病例。全基因组测序表明，携带不确定潜能克隆性造血（CHIP）相关遗传改变的供者细胞在受者骨髓微环境中获得额外的体细胞突变后扩增并最终转化为完全性 AML。10×单细胞 RNA 测序揭示了 DCL 中具有特定转录特征的 GMP 样细胞的丰度。此外，在 DCL 中发现免疫监视受损，包括细胞毒性 T 淋巴细胞（CTL）功能障碍和典型 NK 细胞数量减少。我们的数据为当前 DCL 发病机制的理解提供了有价值的信息。
