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000302323 1001_ $$00000-0001-7942-4495$$aCostea, Julia$$b0
000302323 245__ $$aRole of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia.
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000302323 520__ $$aT-ALL relapses are characterized by chemotherapy resistance, cellular diversity and dismal outcome. To gain a deeper understanding of the mechanisms underlying relapses, we conduct single-cell RNA sequencing on 13 matched pediatric T-ALL patient-derived samples at diagnosis and relapse, along with samples derived from 5 non-relapsing patients collected at diagnosis. This comprehensive longitudinal single-cell study in T-ALL reveals significant transcriptomic diversity. Notably, 11 out of 18 samples exhibit a subpopulation of T-ALL cells with stem-like features characterized by a common set of active regulons, expression patterns and splice isoforms. This subpopulation, accounting for a small proportion of leukemia cells at diagnosis, expands substantially at relapse, indicating resistance to therapy. Strikingly, increased stemness at diagnosis is associated with higher risk of treatment induction failure. Chemotherapy resistance is validated through in-vitro and in-vivo drug testing. Thus, we report the discovery of treatment-resistant stem-like cells in T-ALL, underscoring the potential for devising future therapeutic strategies targeting stemness-related pathways.
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000302323 650_2 $$2MeSH$$aHumans
000302323 650_2 $$2MeSH$$aDrug Resistance, Neoplasm: genetics
000302323 650_2 $$2MeSH$$aPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma: drug therapy
000302323 650_2 $$2MeSH$$aPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma: genetics
000302323 650_2 $$2MeSH$$aPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma: pathology
000302323 650_2 $$2MeSH$$aChild
000302323 650_2 $$2MeSH$$aNeoplastic Stem Cells: metabolism
000302323 650_2 $$2MeSH$$aNeoplastic Stem Cells: pathology
000302323 650_2 $$2MeSH$$aNeoplastic Stem Cells: drug effects
000302323 650_2 $$2MeSH$$aSingle-Cell Analysis
000302323 650_2 $$2MeSH$$aMale
000302323 650_2 $$2MeSH$$aFemale
000302323 650_2 $$2MeSH$$aChild, Preschool
000302323 650_2 $$2MeSH$$aAdolescent
000302323 650_2 $$2MeSH$$aNeoplasm Recurrence, Local: genetics
000302323 650_2 $$2MeSH$$aRecurrence
000302323 650_2 $$2MeSH$$aTranscriptome
000302323 650_2 $$2MeSH$$aAnimals
000302323 650_2 $$2MeSH$$aMice
000302323 650_2 $$2MeSH$$aCell Line, Tumor
000302323 650_2 $$2MeSH$$aGene Expression Regulation, Leukemic
000302323 7001_ $$aRauwolf, Kerstin K$$b1
000302323 7001_ $$0P:(DE-He78)c06a4480eaf1e3373860bfbdf79fb61f$$aZafferani, Pietro$$b2$$udkfz
000302323 7001_ $$aRausch, Tobias$$b3
000302323 7001_ $$0P:(DE-He78)fc0c97c9d01deff15d0a1f0cb8402459$$aMathioudaki, Anna$$b4$$udkfz
000302323 7001_ $$00000-0001-8324-4040$$aZaugg, Judith$$b5
000302323 7001_ $$aSchrappe, Martin$$b6
000302323 7001_ $$0P:(DE-He78)fd9d6272a48791a31f40a854585db572$$aEckert, Cornelia$$b7
000302323 7001_ $$aEscherich, Gabriele$$b8
000302323 7001_ $$00000-0001-6571-6227$$aBourquin, Jean P$$b9
000302323 7001_ $$00000-0003-2890-3191$$aBornhauser, Beat$$b10
000302323 7001_ $$0P:(DE-He78)ca062b8db1ee864e03f0a92897728df3$$aKulozik, Andreas$$b11$$udkfz
000302323 7001_ $$0P:(DE-He78)372b77c2acf8604690a6a325a4e89287$$aKorbel, Jan$$b12$$eLast author$$udkfz
000302323 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-61222-1$$gVol. 16, no. 1, p. 5413$$n1$$p5413$$tNature Communications$$v16$$x2041-1723$$y2025
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