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Programmed Cell Death and Functional Activity of Platelets in Case of Oncohematologic Diseases

A. A. Martyanov1,2,3,4, A. A. Ignatova2, G. S. Svidelskaya2, E. A. Ponomarenko2, S. P. Gambaryan5, A. N. Sveshnikova1,2,4,6, and M. A. Panteleev1,2,4,a*

1Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 109029 Moscow, Russia

2Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117198 Moscow, Russia

3Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia

4Faculty of Physics, Lomonosov Moscow State University, 119991 Moscow, Russia

5Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia

6Department of Normal Physiology, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia

* To whom correspondence should be addressed.

Received July 16, 2020; Revised July 24, 2020; Accepted July 24, 2020
Programmed cell death of non-nucleated blood cells – platelets – could be associated with pathophysiology of oncologic and oncohematologic diseases. It contributes to both bleedings (caused by the thrombocytopenia, which is induced by elimination of the platelets) and thrombosis (caused by the processes of blood coagulation on the surface of phosphatidylserine exposing platelets). Here we characterized functional responses of platelets from the patients with various oncological disorders undergoing chemotherapy and compared them to the platelets from the healthy donors and platelets pre-incubated with apoptosis inducer ABT-737. Some patients exhibited diminished capability of platelets to aggregate. Immunophenotyping of these platelets revealed their pre-activation in comparison to the platelets from the healthy donors. Calcium signaling analysis revealed that in the patient-derived platelets, as well as in the apoptotic platelets, intracellular calcium levels were increased in resting cells. However, moderate level of this increase together with weak expression of phosphatidylserine allows us to assume that apoptotic processes in the circulating platelets from the patients are limited.
KEY WORDS: platelets, apoptosis, chemotherapy, flow cytometry, aggregometry

DOI: 10.1134/S0006297920100144