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@article{1614689,
author = {Jašková, Zuzana and Pavlová, Šárka and Malčíková, Jitka and Brychtová, Yvona and Trbušek, Martin},
article_location = {Oxford},
article_number = {FEB 2020},
doi = {http://dx.doi.org/10.1016/j.leukres.2019.106288},
keywords = {Chronic lymphocytic leukemia; TP53/p53; PRIMA-1(MET); Apoptosis},
language = {eng},
issn = {0145-2126},
journal = {Leukemia Research},
title = {PRIMA-1MET cytotoxic effect correlates with p53 protein reduction in TP53-mutated chronic lymphocytic leukemia cells},
url = {https://www.sciencedirect.com/science/article/pii/S0145212619307337?via%3Dihub},
volume = {89},
year = {2020}
}
TY - JOUR
ID - 1614689
AU - Jašková, Zuzana - Pavlová, Šárka - Malčíková, Jitka - Brychtová, Yvona - Trbušek, Martin
PY - 2020
TI - PRIMA-1MET cytotoxic effect correlates with p53 protein reduction in TP53-mutated chronic lymphocytic leukemia cells
JF - Leukemia Research
VL - 89
IS - FEB 2020
SP - 1-7
EP - 1-7
PB - Pergamon Press
SN - 01452126
KW - Chronic lymphocytic leukemia
KW - TP53/p53
KW - PRIMA-1(MET)
KW - Apoptosis
UR - https://www.sciencedirect.com/science/article/pii/S0145212619307337?via%3Dihub
L2 - https://www.sciencedirect.com/science/article/pii/S0145212619307337?via%3Dihub
N2 - 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.
ER -
JAŠKOVÁ, Zuzana, Šárka PAVLOVÁ, Jitka MALČÍKOVÁ, Yvona BRYCHTOVÁ and Martin TRBUŠEK. PRIMA-1MET cytotoxic effect correlates with p53 protein reduction in TP53-mutated chronic lymphocytic leukemia cells. \textit{Leukemia Research}. Oxford: Pergamon Press, 2020, vol.~89, FEB 2020, p.~1-7. ISSN~0145-2126. Available from: https://dx.doi.org/10.1016/j.leukres.2019.106288.
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