Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00605171" target="_blank" >RIV/68378050:_____/25:00605171 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10490999 RIV/00064165:_____/25:10490999
Result on the web
<a href="https://doi.org/10.3389/fonc.2024.1414950" target="_blank" >https://doi.org/10.3389/fonc.2024.1414950</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fonc.2024.1414950" target="_blank" >10.3389/fonc.2024.1414950</a>
Alternative languages
Result language
angličtina
Original language name
Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML
Original language description
Introduction Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research.Methods We generated a set of transplantable murine PDX models from MDS/AML patients who developed resistance to VEN + AZA and compared the differences in hematopoiesis of the PDX models with primary bone marrow samples at the genetic level. PDX were created in NSGS mice via intraosseal injection of luciferase-encoding Lentivirus-infected MDS/AML primary cells from patient bone marrow. We validated the resistance of PDX-leukemia to VEN and AZA and further tested candidate agents that inhibit the growth of VEN/AZA-resistant AML.Results and discussion Transplantable PDX models for MDS/AML arise with 31 % frequency. The lower frequency of transplantable PDX models is not related to peritransplant lethality of the graft, but rather to the loss of the ability of short-term proliferation of leukemic progenitors after 10 weeks of engraftment. There exist subtle genetic and cytological changes between primary and PDX-AML samples however, the PDX models retain therapy resistance observed in patients. Based on in vitro testing and in vivo validation in PDX models, Panobinostat and Dinaciclib are very promising candidate agents that overcome dual VEN + AZA resistance.
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
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
Frontiers in Oncology
ISSN
2234-943X
e-ISSN
2234-943X
Volume of the periodical
14
Issue of the periodical within the volume
07 Jan
Country of publishing house
CH - SWITZERLAND
Number of pages
11
Pages from-to
1414950
UT code for WoS article
001400544800001
EID of the result in the Scopus database
2-s2.0-85215500840