epigenetics

Hypomethylating Agents in Oncohematology

REVIEWS , , , ,

AD Shirin, OYu Baranova

NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Anton Dmitrievich Shirin, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-28-24; e-mail: shirin-anton@mail.ru

For citation: Shirin AD, Baranova OYu. Hypomethylating Agents in Oncohematology. Clinical oncohematology. 2016;9(4):369–82 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-369-382

ABSTRACT

The review describes epigenetic processes, including methylation of nuclear and mitochondrial DNA, as well as RNA. It dwells on mechanisms of demethylation and corresponding medicinal products. It presents detailed information on results of numerous large randomized studies intended to evaluate hypomethylating agents (azanucleosides). Special attention is paid to outcomes of azanucleoside therapy in patients with acute myeloid leukemias. The article describes several prognostic systems and treatment algorithms for myelodysplastic syndromes. Two azanucleosides have been approved in Russia to date: azacitidine (for SQ administration) and decitabine (for IV administration). International authors analyze the experience in oral and subcutaneous administration of decitabine. However, the problem of off-label use of hypomethylating agents is still open. The review gives a brief description of ongoing clinical trials with azanucleosides.

Keywords: epigenetics, acute myeloid leukemias, myelodysplastic syndromes, azacitidine, decitabine, hypomethylating agents, azanucleosides.

Received: May 10, 2016

Accepted: May 20, 2016

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Epigenetics in Oncohematology: Brief Review

REVIEWS , , , ,

AD Shirin, GI Kaletin, OYu Baranova

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Shirin Anton Dmitrievich, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-28-24; e-mail: shirin-anton@mail.ru

For citation: Shirin AD, Kaletin GI, Baranova OYu. Epigenetics in Oncohematology: Brief Review. Clinical oncohematology. 2015;8(1):26–30 (In Russ).

ABSTRACT

Objective. To discuss historical aspects of epigenetics as an independent branch of biology, as well as to describe post-translational modifications of DNA and histones (PTMs) as epigenetic events.

Methods. Review of fundamentals of epigenetics in topical articles and abstracts: DNA methylation, histones acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation in the development of oncological disorders. The effect of so-called interfering RNA on epigenetic processes has drawn much attention in recent years. The RNA interference (RNAi) can be used to detect epigenetic regulators for the purpose of potential pharmacologic effect on tumor cells. The significance of small I-BET and JQ1 molecules in the antitumor response is considered. The role of BET proteins in hematologic malignancies is discussed separately.

Conclusions. At present, DNA methyltransferase inhibitors (hypomethylating agents) and histone deacetylase inhibitors (which represent a brand new approach, an epigenetic therapy) are used for the treatment of hematopoietic neoplasms.

Keywords: epigenetics, RNA interference, BET proteins, methylation, deacetylation.

Received: December 2, 2014

Accepted: December 12, 2014

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