CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CAR-T 细胞与 blinatumomab 治疗后 KMT2A 野生型谱系转换白血病的克隆起源
英文原题：Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy.
查看英文原题
Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy.
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中文摘要
接受抗CD19治疗的急性淋巴细胞白血病（ALL）儿童偶尔会发展为急性髓系白血病（AML）。此类谱系转换白血病的克隆起源1-4仍未明确。在此，我们重建了一名女孩体内多种白血病的系统发育，该女孩在多次复发的ALL后接受了抗CD19细胞和抗体治疗，随后发展为AML。全基因组测序明确揭示AML源自最初的ALL，并带有在出现前即可检测到的不同驱动突变。广泛的先前多样化和随后的克隆选择是这一致命谱系转换的基础。对原发性白血病和复发的基因组监测可能预测治疗耐药性，尤其是关于抗CD19治疗。
展开英文摘要原文
Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias 1-4 remains unresolved.
Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence.
Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment.
论文信息
- 作者
- Coorens THH、Collord G、Treger TD、Adams S、Mitchell E、Newman B、Getz G、Godfrey AL
- 第一作者单位
- Broad Institute of MIT and Harvard, Cambridge, MA, USA. tcoorens@broadinstitute.org.United Kingdom
- 通讯作者单位
- Wellcome Sanger Institute, Hinxton, UK. sb31@sanger.ac.uk.United Kingdom
- 文献类型
- 非美国政府资助研究
- 期刊
- Nature cancer2023 Aug
- 原文标识
- PubMed 37474833 · DOI 10.1038/s43018-023-00604-0
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