RUNX1 mutations contribute to the progression of MDS due to disruption of antitumor cellular defense: a study on patients with lower-risk MDS
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F22%3A00077623" target="_blank" >RIV/00159816:_____/22:00077623 - isvavai.cz</a>
Alternative codes found
RIV/00023736:_____/22:00013397 RIV/00064165:_____/22:10444827 RIV/00216208:11110/22:10444827 RIV/00216208:11310/22:10444827 and 2 more
Result on the web
<a href="https://www.nature.com/articles/s41375-022-01584-3" target="_blank" >https://www.nature.com/articles/s41375-022-01584-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41375-022-01584-3" target="_blank" >10.1038/s41375-022-01584-3</a>
Alternative languages
Result language
angličtina
Original language name
RUNX1 mutations contribute to the progression of MDS due to disruption of antitumor cellular defense: a study on patients with lower-risk MDS
Original language description
Patients with lower-risk myelodysplastic syndromes (LR-MDS) have a generally favorable prognosis; however, a small proportion of cases progress rapidly. This study aimed to define molecular biomarkers predictive of LR-MDS progression and to uncover cellular pathways contributing to malignant transformation. The mutational landscape was analyzed in 214 LR-MDS patients, and at least one mutation was detected in 137 patients (64%). Mutated RUNX1 was identified as the main molecular predictor of rapid progression by statistics and machine learning. To study the effect of mutated RUNX1 on pathway regulation, the expression profiles of CD34 + cells from LR-MDS patients with RUNX1 mutations were compared to those from patients without RUNX1 mutations. The data suggest that RUNX1-unmutated LR-MDS cells are protected by DNA damage response (DDR) mechanisms and cellular senescence as an antitumor cellular barrier, while RUNX1 mutations may be one of the triggers of malignant transformation. Dysregulated DDR and cellular senescence were also observed at the functional level by detecting gamma H2AX expression and beta-galactosidase activity. Notably, the expression profiles of RUNX1-mutated LR-MDS resembled those of higher-risk MDS at diagnosis. This study demonstrates that incorporating molecular data improves LR-MDS risk stratification and that mutated RUNX1 is associated with a suppressed defense against LR-MDS progression.
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
<a href="/en/project/NV18-03-00227" target="_blank" >NV18-03-00227: Identification and monitoring of prognostic and predictive molecular markers in patients with low risk myelodysplastic syndrome</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia
ISSN
0887-6924
e-ISSN
1476-5551
Volume of the periodical
36
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
1898-1906
UT code for WoS article
000790084900001
EID of the result in the Scopus database
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