Single-cell heterogeneity and dynamic evolution of Ph-like acute lymphoblastic leukemia patient with novel TPR-PDGFRB fusion gene
Single-cell heterogeneity and dynamic evolution of Ph-like acute lymphoblastic leukemia patient with novel TPR-PDGFRB fusion gene
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DOI：
10.1186/s40164-023-00380-8
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发表时间：
2023
影响因子：
10.9
通讯作者：
Jinsong Yan
中科院分区：
文献类型：
--
作者：
Xuehong Zhang;Zhijie Hou;Dan Huang;Furong Wang;Beibei Gao;Chengtao Zhang;Dong Zhou;Jiacheng Lou;Haina Wang;Yuan Gao;Zhijie Kang;Ying Lu;Quentin Liu;Jinsong Yan
AbstractPhiladelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a refractory and recurrent subtype of B-cell ALL enriched with kinase-activating rearrangements. Incomplete understanding of the heterogeneity within the tumor cells presents a major challenge for the diagnosis and therapy of Ph-like ALL. Here, we exhibited a comprehensive cell atlas of one Ph-like ALL patient with a novel TPR-PDGFRB fusion gene at diagnosis and relapse by using single-cell RNA sequencing (scRNA-seq). Twelve heterogeneous B-cell clusters, four with strong MKI67 expression indicating highly proliferating B cells, were identified. A relapse-enriched B-cell subset associated with poor prognosis was discovered, implicating the transcriptomic evolution during disease progression. Integrative single-cell analysis was performed on Ph-like ALL and Ph+ ALL patients, and revealed Ph-like specific B-cell subpopulations and shared malignant B cells characterized by the ectopic expression of the inhibitory receptor CLEC2D. Collectively, scRNA-seq of Ph-like ALL with a novel TPR-PDGFRB fusion gene provides valuable insights into the underlying heterogeneity associated with disease progression and offers useful information for the development of immunotherapeutic techniques in the future.
