The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia.
Akiko UrabeSung-Gi ChiYosuke MinamiPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- acute myeloid leukemia
- clinical trial
- stem cells
- induced apoptosis
- copy number
- dna methylation
- palliative care
- single molecule
- gene expression
- cell cycle arrest
- genome wide
- prostate cancer
- circulating tumor
- small molecule
- working memory
- low grade
- rectal cancer
- cell proliferation
- radical prostatectomy
- cell death
- minimally invasive
- replacement therapy
- double blind