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@ARTICLE{Costea:302323,
author = {J. Costea and K. K. Rauwolf and P. Zafferani$^*$ and T.
Rausch and A. Mathioudaki$^*$ and J. Zaugg and M. Schrappe
and C. Eckert$^*$ and G. Escherich and J. P. Bourquin and B.
Bornhauser and A. Kulozik$^*$ and J. Korbel$^*$},
title = {{R}ole of stem-like cells in chemotherapy resistance and
relapse in pediatric {T}-cell acute lymphoblastic leukemia.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01318},
pages = {5413},
year = {2025},
note = {#LA:B480#},
abstract = {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.},
keywords = {Humans / Drug Resistance, Neoplasm: genetics / Precursor
T-Cell Lymphoblastic Leukemia-Lymphoma: drug therapy /
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: genetics /
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: pathology
/ Child / Neoplastic Stem Cells: metabolism / Neoplastic
Stem Cells: pathology / Neoplastic Stem Cells: drug effects
/ Single-Cell Analysis / Male / Female / Child, Preschool /
Adolescent / Neoplasm Recurrence, Local: genetics /
Recurrence / Transcriptome / Animals / Mice / Cell Line,
Tumor / Gene Expression Regulation, Leukemic},
cin = {B270 / B450 / BE01 / A400 / B480},
ddc = {500},
cid = {I:(DE-He78)B270-20160331 / I:(DE-He78)B450-20160331 /
I:(DE-He78)BE01-20160331 / I:(DE-He78)A400-20160331 /
I:(DE-He78)B480-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40579412},
doi = {10.1038/s41467-025-61222-1},
url = {https://inrepo02.dkfz.de/record/302323},
}