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Review
. 2021 Oct 15;11(5):458-471.
eCollection 2021.

Systematic review of epigenetic targets in acute myeloid leukemia

Shweta Verma  1 , Himanshu Dhanda  1 , Amitabh Singh  2 , Bhavika Rishi  3 , Pranay Tanwar  4 , Sumita Chaudhry  5 , Fouzia Siraj  3 , Aroonima Misra  3
Affiliations
Review

Systematic review of epigenetic targets in acute myeloid leukemia

Shweta Verma et al. Am J Blood Res. .

Abstract

Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and worse outcomes. The current diagnostic classification of AML offers best curative intent, the outcomes are not usually those that are expected at the start of therapy. This is partly attributed to the complex mechanism of leukemogenesis and resistance to chemotherapy. The underlying genetic mechanism of resistance is as complex as is the disease etiopathogenesis. Recent advances in therapy of drug resistant AML highlight the role of epigenetic targets. New FDA approved targeted therapy has also provided some evidence at improving outcomes in clinical trials. This review provides a detailed review of FDA approved targets and ongoing clinical trials for targeting CRISPER, CAR-T and other intestinal modalities for approach to epigenetictargets. However, this group of epigenetic targeted therapy needs more validation to prove its clinical efficacy. A systematic review of all published research on these targets, investigational agents and FDA approved targeted therapy summarizes this evidence. It also takes us through a brief review of mechanism of action and targets for therapy.

Keywords: Acute myeloid leukemia; epigenetic targets; histone deacetylation; methylation; targeted therapy; ubiquitination.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
DNA Methylation.
Figure 2
Figure 2
Enzymatic activity of mutated and wild type IDH enzyme.
Figure 3
Figure 3
The interactions and effects of EZH2 in regulation of transcriptional repression.
Figure 4
Figure 4
Mechanism of action of DOT1L and infuences of other epigenetic modifications.
Figure 5
Figure 5
LSD1 as a transcriptional co-repressor in H3K4 (Daniela Magliulo et al., 2018).
Figure 6
Figure 6
Regulation of NF-кB by BRD4.
Figure 7
Figure 7
Mechanism of action of BET inhibitor. A. BET protein regulates transcription of gene related to various functions as shown. The BET family member, BRD4 plays important role in oncogenic expression of MYC in malignancies. B. BET inhibitors release BRDs from chromatin, reduce RNA-Pol II blocking transcription of downstream gene. (Diana Reyes-Garau et al., 2019).
See this image and copyright information in PMC

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