Wild-type p53-induced phosphatase sensitizes acute myeloid leukemia cells to conventional chemotherapy

  • Vasily Golotin Laboratory of Molecular Medicine, Institute of Cytology of the Russian Academy of Sciences, Tikhoretskiy pr., 4, Saint Petersburg, 194064, Russian Federation https://orcid.org/0000-0003-0385-2463
  • Ekaterina Belotserkovskaya Almazov Federal Medical Research Centre, ul. Akkuratova, 2, 197341, Saint Petersburg, Russian Federation https://orcid.org/0000-0003-3985-9552
  • Larisa Girshova Almazov Federal Medical Research Centre, ul. Akkuratova, 2, 197341, Saint Petersburg, Russian Federation https://orcid.org/0000-0002-0559-9556
  • Alexey Petukhov Almazov Federal Medical Research Centre, ul. Akkuratova, 2, 197341, Saint Petersburg, Russian Federation https://orcid.org/0000-0002-7298-5238
  • Andrey Zaritsky Almazov Federal Medical Research Centre, ul. Akkuratova, 2, 197341, Saint Petersburg, Russian Federation
  • Oleg Demidov Laboratory of Molecular Medicine, Institute of Cytology of the Russian Academy of Sciences, Tikhoretskiy pr., 4, Saint Petersburg, 194064, Russian Federation; INSERM UMR1231, Laboratory of Excellence LipSTIC and label Ligue Nationale contre le Cancer, 7 Boulevard Jeanne d'Arc, BP 27877, 21078, Dijon Cedex, France https://orcid.org/0000-0003-4323-7174

Abstract

Recently wild-type p53-induced phosphatase was implicated in the pathogenesis of acute myeloid leukemia (AML) and “pre-leukemia” myeloproliferative conditions. Here we decided to check how the strategy directed to phosphatase inhibition affected sensitivity to conventional chemotherapy. All experiments were conducted on AML cell lines cultivated in vitro. The levels of wild-type p53-induced phosphatase vary in different AML cell lines. The chemical compound GSK2830371 reduced levels of phosphatase and diminished its activity. GSK2830371 did not significantly change the cell cycle distribution of AML cells when used alone or in combination with the anti-cancer chemotherapeutic drug Cytosar but increased caspase-dependent PARP1 cleavage. In contrast with previous studies, we did not observe the negative effect of phosphatase activity inhibition and depletion on cells when a chemical inhibitor was used as monotherapy. Using a combination of GSK2830371 with Cytosar we were able to reduce the threshold of chemotherapy-dependent cytotoxicity and more efficiently eliminate leukemic cells. We propose considering inhibition of wild-type p53-induced phosphatase as a prospective strategy in improving anti-AML therapy.

Keywords:

leukemia, AML, chemotherapy, cytarabine

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Published
2021-11-12
How to Cite
Golotin, V., Belotserkovskaya, E., Girshova, L., Petukhov, A., Zaritsky, A., & Demidov, O. (2021). Wild-type p53-induced phosphatase sensitizes acute myeloid leukemia cells to conventional chemotherapy. Biological Communications, 66(3), 268–273. https://doi.org/10.21638/spbu03.2021.308
Section
Brief communications