Therapeutic Opportunities of Targeting Canonical and Noncanonical PcG TrxG Functions in Acute Myeloid Leukemia

Transcriptional deregulation is a key driver of acute myeloid leukemia (AML), a heterogeneous blood cancer with poor survival rates. Polycomb group (PcG) and Trithorax group (TrxG) genes, originally identified in Drosophila melanogaster several decades ago as master regulators of cellular identity a...

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Bibliographic Details
Published in:Annual review of genomics and human genetics 2021-08, Vol.22 (1), p.103-125
Main Authors: Zeisig, Bernd B, So, Chi Wai Eric
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Animals
antagonistic pleiotropy
Drosophila melanogaster
Drug resistance
Epigenetics
EZH2
Humans
Lethality
Leukemia
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
MLL
Myeloid leukemia
Pleiotropy
Polycomb group proteins
Polycomb repressive complex
Polycomb-Group Proteins - genetics
synthetic lethality
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Summary:Transcriptional deregulation is a key driver of acute myeloid leukemia (AML), a heterogeneous blood cancer with poor survival rates. Polycomb group (PcG) and Trithorax group (TrxG) genes, originally identified in Drosophila melanogaster several decades ago as master regulators of cellular identity and epigenetic memory, not only are important in mammalian development but also play a key role in AML disease biology. In addition to their classical canonical antagonistic transcriptional functions, noncanonical synergistic and nontranscriptional functions of PcG and TrxG are emerging. Here, we review the biochemical properties of major mammalian PcG and TrxG complexes and their roles in AML disease biology, including disease maintenance as well as drug resistance. We summarize current efforts on targeting PcG and TrxG for treatment of AML and propose rational synthetic lethality and drug-induced antagonistic pleiotropy options involving PcG and TrxG as potential new therapeutic avenues for treatment of AML.
ISSN:1527-8204
1545-293X
DOI:10.1146/annurev-genom-111120-102443