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Review
. 2021 Jul 8;22(14):7340.
doi: 10.3390/ijms22147340.

Gene Transcription as a Therapeutic Target in Leukemia

Alvina I Khamidullina  1 , Ekaterina A Varlamova  1 , Nour Alhuda Hammoud  2 , Margarita A Yastrebova  1 , Alexandra V Bruter  1
Affiliations
Review

Gene Transcription as a Therapeutic Target in Leukemia

Alvina I Khamidullina et al. Int J Mol Sci. .

Abstract

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.

Keywords: cell death; drug design; leukemia; targeted antitumor therapy; transcription.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of HDAC inhibitors. (A) The active group is hydroxamic acid (red) which binds to the zinc ion in HDAC [24]. (B) The zinc-binding moiety is highlighted in red: ortho-NH2 group and the carbonyl oxygen chelate Zn. CAP is a hydrophobic group for protein surface recognition [34]. (C) The disulfide bond in romidepsin is reduced by glutathione to form an active compound. The reduced romidepsin forms a covalent disulfide bond with the sole cysteine residue in the HDAC pocket [35]. The structures were designed by ChemDraw®, a product of PerkinElmer.
See this image and copyright information in PMC

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