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Review

The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia

by
Akiko Urabe
,
SungGi Chi
and
Yosuke Minami
*
Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-8577, Chiba, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(4), 3727; https://doi.org/10.3390/ijms24043727
Submission received: 24 December 2022 / Revised: 30 January 2023 / Accepted: 9 February 2023 / Published: 13 February 2023
(This article belongs to the Special Issue Molecular Biology and Immunological Advances in Hematological Malignancies)
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Abstract

Hypomethylating agents (HMAs) have been used for decades in the treatment of hematologic neoplasms, and now, have gathered attention again in terms of their combination with potent molecular-targeted agents such as a BCL-6 inhibitor venetoclax and an IDH1 inhibitor ivosidenib, as well as a novel immune-checkpoint inhibitor (anit-CD47 antibody) megrolimab. Several studies have shown that leukemic cells have a distinct immunological microenvironment, which is at least partially due to genetic alterations such as the TP53 mutation and epigenetic dysregulation. HMAs possibly improve intrinsic anti-leukemic immunity and sensitivity to immune therapies such as PD-1/PD-L1 inhibitors and anti-CD47 agents. This review describes the immuno-oncological backgrounds of the leukemic microenvironment and the therapeutic mechanisms of HMAs, as well as current clinical trials of HMAs and/or venetoclax-based combination therapies.
Keywords: hypomethylating agents; acute myeloid leukemia; PD-1; CD47 hypomethylating agents; acute myeloid leukemia; PD-1; CD47

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MDPI and ACS Style

Urabe, A.; Chi, S.; Minami, Y. The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia. Int. J. Mol. Sci. 2023, 24, 3727. https://doi.org/10.3390/ijms24043727

AMA Style

Urabe A, Chi S, Minami Y. The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia. International Journal of Molecular Sciences. 2023; 24(4):3727. https://doi.org/10.3390/ijms24043727

Chicago/Turabian Style

Urabe, Akiko, SungGi Chi, and Yosuke Minami. 2023. "The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia" International Journal of Molecular Sciences 24, no. 4: 3727. https://doi.org/10.3390/ijms24043727

APA Style

Urabe, A., Chi, S., & Minami, Y. (2023). The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia. International Journal of Molecular Sciences, 24(4), 3727. https://doi.org/10.3390/ijms24043727

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