Dose and drug changes in chronic lymphocytic leukemia cell response in vitro: A comparison of standard therapy regimens with two novel cyclin‑dependent kinase inhibitors

Kubczak,Małgorzata; Szustka,Aleksandra; Błoński,Jerzy Z.; Gucký,Tomaš; Misiewicz,Małgorzata; Krystof,Vladmir; Robak,Paweł; Rogalińska,Małgorzata

doi:10.3892/mmr.2019.10007

Dose and drug changes in chronic lymphocytic leukemia cell response in vitro: A comparison of standard therapy regimens with two novel cyclin‑dependent kinase inhibitors

Authors:
- Małgorzata Kubczak
- Aleksandra Szustka
- Jerzy Z. Błoński
- Tomaš Gucký
- Małgorzata Misiewicz
- Vladmir Krystof
- Paweł Robak
- Małgorzata Rogalińska
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Affiliations: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90‑236 Lodz, Poland, Department of Hematology, Medical University of Lodz, 93‑510 Lodz, Poland, Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, 78371 Olomouc, Czech Republic, Laboratory of Growth Regulators, Faculty of Science, Palacký University and Institute of Experimental Botany AS CR, 78371 Olomouc, Czech Republic, Department of Experimental Hematology, Medical University of Lodz, 93‑510 Lodz, Poland
Published online on: March 5, 2019 https://doi.org/10.3892/mmr.2019.10007
Pages: 3593-3603
Copyright: © Kubczak et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Chronic lymphocytic leukemia (CLL) treatment is improving; however, some patients do not respond to therapy. Due to the high heterogeneity in disease development, there is an urgent need for personalization of therapy. In the present study, the response of leukemic mononuclear cells to anticancer drugs used for CLL treatment (cladribine + mafosfamide; CM or CM combined with rituximab; RCM) was compared with the response to new cyclin‑dependent kinase (CDK) inhibitors: BP14 and BP30. Viable apoptotic and necrotic cells were quantified by flow cytometry using propidium iodide and Yo‑Pro stains. CDK inhibitors were studied in several doses to determine the reduction of necrosis and simultaneous increase of apoptosis in leukemic cell incubations with anticancer agents. The distinct cell response to applied doses/anticancer agents was observed. Results obtained in the current manuscript confirmed that modulation of doses is important. This was particularly indicated in results obtained at 24 h of cells incubation with anticancer agent. While an important time for analysis of anticancer response efficacy (monitoring of apoptosis induction potential) seems to be 48 h of cells exposition to anticancer agents. High variability in response to the drugs revealed that both the nature and the dose of the anticancer agents could be important in the final effect of the therapy. The present findings support the thesis that personalized medicine, before drug administration in the clinic, could be important to avoid the application of ineffective therapy.

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