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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Abstract Philadelphia 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 flexcon reverse osmosis water storage tank 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 dea eyewear 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.