High-Risk neuroblastoma therapeutics Topotecan and 13-cis-Retinoic acid modulate autophagy and induce DNA damage response in hematopoietic stem cells and monocytes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023698%3A_____%2F25%3AN0000013" target="_blank" >RIV/00023698:_____/25:N0000013 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10504427 RIV/00159816:_____/25:00082230 RIV/00216224:14110/25:00144750 RIV/00064165:_____/25:10504427
Result on the web
<a href="https://www.nature.com/articles/s41598-025-19454-0" target="_blank" >https://www.nature.com/articles/s41598-025-19454-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-025-19454-0" target="_blank" >10.1038/s41598-025-19454-0</a>
Alternative languages
Result language
angličtina
Original language name
High-Risk neuroblastoma therapeutics Topotecan and 13-cis-Retinoic acid modulate autophagy and induce DNA damage response in hematopoietic stem cells and monocytes
Original language description
Autologous hematopoietic stem and progenitor cell (HSPC) transplantation is performed after myeloablation in cancer treatment to restore blood cell production and support immune recovery. Despite its success in achieving survivorship, many recipients later suffer from recurrent infections and pulmonary complications. The mechanisms driving the complications after HSPC transplantation later in life are unknown. However, the induction and/or maintenance therapeutics might be driving the negative outcomes in treated patients. We investigated the effects of the cancer therapeutics topotecan and 13-cis-retinoic acid (13cisRA) on cell phenotype and functions of HSPCs isolated from cord blood and primary monocytes from adult donors. In HSPCs, 13cisRA reduced autophagy and lysosomal activity, triggered a DNA damage response through increased gamma H2A.X and CDKN2 expression (including the spliced p14ARF isoform), and upregulated the epigenetic regulator SIRT3. 13cisRA also activated primary monocytes, inducing CXCL8 and CCL2 production. By contrast, topotecan had no effects on mature monocytes but induced DNA damage, metabolic remodeling, and epigenetic alterations in HSPCs. These changes included increased CDKN1A expression, higher gamma H2A.X-positive cell frequency, autophagy activation, and SIRT1 upregulation. The differential effects of 13cisRA and topotecan on HSPCs and monocytes might underlie the long-term complications of autologous HSPC transplantation. By modulating DNA damage, autophagy, and epigenetic pathways, these therapies could influence hematopoietic recovery and immune reconstitution, offering insights for improving transplantation outcomes.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
<a href="/en/project/NW24J-09-00054" target="_blank" >NW24J-09-00054: New quality and fitness evaluation methods of CD34+ cells and CD34-derived myeloid cells from mobilized blood</a><br>
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
SCIENTIFIC REPORTS
ISSN
2045-2322
e-ISSN
2045-2322
Volume of the periodical
15
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
18
Pages from-to
35723
UT code for WoS article
001593359600030
EID of the result in the Scopus database
2-s2.0-105018648560