Advancements and Future Prospects in Molecular Targeted and siRNA Therapies for Chronic Myeloid Leukemia
Vera Vysochinskaya,
Olesya Dovbysh,
Andrey Gorshkov,
Alexandra Brodskaia,
Michael Dubina,
Andrey Vasin,
Yana Zabrodskaya
Affiliations
Vera Vysochinskaya
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia
Olesya Dovbysh
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia
Andrey Gorshkov
Smorodintsev Research Institute of Influenza, Russian Ministry of Health, 15/17 Ulitsa Prof. Popova, 197376 St. Petersburg, Russia
Alexandra Brodskaia
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia
Michael Dubina
Russian Academy of Sciences, 14 Leninskiy pr., 119991 Moscow, Russia
Andrey Vasin
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia
Yana Zabrodskaya
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia
Chronic myeloid leukemia (CML) is an oncological myeloproliferative disorder that accounts for 15 to 20% of all adult leukemia cases. The molecular basis of this disease lies in the formation of a chimeric oncogene BCR–ABL1. The protein product of this gene, p210 BCR–ABL1, exhibits abnormally high constitutive tyrosine kinase activity. Over recent decades, several targeted tyrosine kinase inhibitors (TKIs) directed against BCR–ABL1 have been developed and introduced into clinical practice. These inhibitors suppress BCR–ABL1 activity through various mechanisms. Furthermore, the advent of RNA interference technology has enabled the highly specific inhibition of BCR–ABL1 transcript expression using small interfering RNA (siRNA). This experimental evidence opens avenues for the development of a novel therapeutic strategy for CML, termed siRNA therapy. The review delves into molecular genetic mechanisms underlying the pathogenesis of CML, challenges in CML therapy, potential molecular targets for drug development, and the latest results from the application of siRNAs in in vitro and in vivo CML models.
