Pharmacologic Targeting of Chromatin Modulators As Therapeutics of Acute Myeloid Leukemia

Frontiers in Oncology
Rui Lu, Gang Greg Wang

Abstract

Acute myeloid leukemia (AML), a common hematological cancer of myeloid lineage cells, generally exhibits poor prognosis in the clinic and demands new treatment options. Recently, direct sequencing of samples from human AMLs and pre-leukemic diseases has unveiled their mutational landscapes and significantly advanced the molecular understanding of AML pathogenesis. The newly identified recurrent mutations frequently "hit" genes encoding epigenetic modulators, a wide range of chromatin-modifying enzymes and regulatory factors involved in gene expression regulation, supporting aberration of chromatin structure and epigenetic modification as a main oncogenic mechanism and cancer-initiating event. Increasing body of evidence demonstrates that chromatin modification aberrations underlying the formation of blood cancer can be reversed by pharmacological targeting of the responsible epigenetic modulators, thus providing new mechanism-based treatment strategies. Here, we summarize recent advances in development of small-molecule inhibitors specific to chromatin factors and their potential applications in the treatment of genetically defined AMLs. These compounds selectively inhibit various subclasses of "epigenetic writers" (such as his...Continue Reading

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Citations

May 31, 2019·Cellular and Molecular Life Sciences : CMLS·Jie LiGang Greg Wang
Sep 27, 2019·Frontiers in Oncology·Judith SchütteChristine Eisfeld
Nov 5, 2019·Frontiers in Pediatrics·Thomas Mercher, Juerg Schwaller
Jun 6, 2019·Frontiers in Oncology·Danielle GolubDimitris G Placantonakis
Jun 14, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Nok-Hei Mickey Wong, Chi Wai Eric So
Apr 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Nichole OwenAmanda K McCullough
May 19, 2021·Nature Reviews. Cancer·Shuai ZhaoGang Greg Wang

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Datasets Mentioned

BETA
SGC0946

Methods Mentioned

BETA
histone acetylation
MDS
acetylations
acetylation

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