Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies

SIMPLE SUMMARY: This review summarizes the current findings about the cellular roles of protein arginine methyltransferases (PRMTs) in the formation of blood cells from stem cell progenitors and in different blood cancers such as leukemia and lymphoma. The work also provides a substantial insight into the development and the use of PRMT inhibitors for the treatment of hematological cancers. This review aims to show the research community that targeting PRMTs could be a novel and promising therapeutic approach for these diseases. ABSTRACT: Arginine methylation is a common post-translational modification affecting protein activity and the transcription of target genes when methylation occurs on histone tails. There are nine protein arginine methyltransferases (PRMTs) in mammals, divided into subgroups depending on the methylation they form on a molecule of arginine. During the formation and maturation of the different types of blood cells, PRMTs play a central role by controlling cell differentiation at the transcriptional level. PRMT enzymatic activity is necessary for many cellular processes in hematological malignancies, such as the activation of cell cycle and proliferation, inhibition of apoptosis, DNA repair processes, RNA splicing, and transcription by methylating histone tails’ arginine. Chemical tools have been developed to inhibit the activity of PRMTs and have been tested in several models of hematological malignancies, including primary samples from patients, xenografts into immunodeficient mice, mouse models, and human cell lines. They show a significant effect by reducing cell viability and increasing the overall survival of mice. PRMT5 inhibitors have a strong therapeutic potential, as phase I clinical trials in hematological malignancies that use these molecules show promising results, thus, underlining PRMT inhibitors as useful therapeutic tools for cancer treatment in the future.