PRIMA-1MET cytotoxic effect correlates with p53 protein reduction in TP53-mutated chronic lymphocytic leukemia cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00115275" target="_blank" >RIV/00216224:14110/20:00115275 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/20:00072715
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0145212619307337?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0145212619307337?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.leukres.2019.106288" target="_blank" >10.1016/j.leukres.2019.106288</a>
Alternative languages
Result language
angličtina
Original language name
PRIMA-1MET cytotoxic effect correlates with p53 protein reduction in TP53-mutated chronic lymphocytic leukemia cells
Original language description
TP53 gene defects represent the most unfavorable prognostic factor in chronic lymphocytic leukemia (CLL). Although recently introduced small-molecule B-cell receptor signalling inhibitors have revolutionized CLL treatment, data for ibrutinib still point to impaired prognosis for TP53-affected patients. Among cancer-associated TP53 mutations, missense substitutions predominate and typically result in a high mutated-p53 protein level. Therefore, rescuing the p53 tumor suppressor function through specific small molecules restoring p53 wild-type (wt) conformation represents an attractive therapeutic strategy for cancer patients with TP53 missense mutations. We tested the effect of mutated-p53 reactivating molecule PRIMA-1(MET) in 62 clinical CLL samples characterized for TP53 mutations and p53 protein level. At the subtle PRIMA-1(MET) concentrations (1-4 mu M), most samples manifested concentration-dependent viability decrease and, conversely, apoptosis induction, with the response being similar in both the TP53-mutated and TP53-wt groups, as well as in the TP53-mutated samples with p53 protein stabilization and without it. PRIMA-1(MET) was able to reduce mutated p53 protein in a proportion of TP53-mutated CLL samples, and this reduction correlated with a significantly stronger viability decrease and apoptosis induction than samples with stable p53 levels. CLL cells are mostly sensitive to PRIMA-1(MET) apart from those with stable mutated p53.
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
30205 - Hematology
Result continuities
Project
—
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia Research
ISSN
0145-2126
e-ISSN
1873-5835
Volume of the periodical
89
Issue of the periodical within the volume
FEB 2020
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
1-7
UT code for WoS article
000509785500002
EID of the result in the Scopus database
2-s2.0-85077381271