Home > Publications database > Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia. > print

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024 7 _ |a 10.1038/s41467-025-61222-1
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082 _ _ |a 500
100 1 _ |a Costea, Julia
|0 0000-0001-7942-4495
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245 _ _ |a Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia.
260 _ _ |a [London]
|c 2025
|b Springer Nature
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520 _ _ |a T-ALL relapses are characterized by chemotherapy resistance, cellular diversity and dismal outcome. To gain a deeper understanding of the mechanisms underlying relapses, we conduct single-cell RNA sequencing on 13 matched pediatric T-ALL patient-derived samples at diagnosis and relapse, along with samples derived from 5 non-relapsing patients collected at diagnosis. This comprehensive longitudinal single-cell study in T-ALL reveals significant transcriptomic diversity. Notably, 11 out of 18 samples exhibit a subpopulation of T-ALL cells with stem-like features characterized by a common set of active regulons, expression patterns and splice isoforms. This subpopulation, accounting for a small proportion of leukemia cells at diagnosis, expands substantially at relapse, indicating resistance to therapy. Strikingly, increased stemness at diagnosis is associated with higher risk of treatment induction failure. Chemotherapy resistance is validated through in-vitro and in-vivo drug testing. Thus, we report the discovery of treatment-resistant stem-like cells in T-ALL, underscoring the potential for devising future therapeutic strategies targeting stemness-related pathways.
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Drug Resistance, Neoplasm: genetics
|2 MeSH
650 _ 2 |a Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: drug therapy
|2 MeSH
650 _ 2 |a Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: genetics
|2 MeSH
650 _ 2 |a Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: pathology
|2 MeSH
650 _ 2 |a Child
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: pathology
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: drug effects
|2 MeSH
650 _ 2 |a Single-Cell Analysis
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Child, Preschool
|2 MeSH
650 _ 2 |a Adolescent
|2 MeSH
650 _ 2 |a Neoplasm Recurrence, Local: genetics
|2 MeSH
650 _ 2 |a Recurrence
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Leukemic
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700 1 _ |a Rauwolf, Kerstin K
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700 1 _ |a Zafferani, Pietro
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700 1 _ |a Rausch, Tobias
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700 1 _ |a Mathioudaki, Anna
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700 1 _ |a Zaugg, Judith
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700 1 _ |a Schrappe, Martin
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700 1 _ |a Eckert, Cornelia
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700 1 _ |a Escherich, Gabriele
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700 1 _ |a Bourquin, Jean P
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700 1 _ |a Bornhauser, Beat
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700 1 _ |a Kulozik, Andreas
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700 1 _ |a Korbel, Jan
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773 _ _ |a 10.1038/s41467-025-61222-1
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