[Research Progress on Epigenetic Regulation of the Leukemia Microenvironment --Review]

Area of Science:

• Hematology
• Immunology
• Epigenetics

Background:

• Leukemia development and progression are influenced by both leukemia cell-intrinsic factors and the bone marrow microenvironment (BMM).
• Leukemic cells actively remodel the immune BMM, leading to T-cell dysfunction, impaired NK-cell function, and myeloid cell polarization, fostering disease progression and resistance.
• Epigenetic mechanisms regulate key processes in leukemia, including antigen presentation, immune checkpoint expression, and interferon signaling, impacting immune evasion and immunotherapy response.

Purpose of the Study:

• To review the interplay between immune microenvironment remodeling, epigenetic regulation, drug resistance, and relapse in leukemia.
• To outline immunosuppressive networks and their epigenetic underpinnings in various leukemia subtypes.
• To discuss advances and challenges in combining epigenetic therapies with other treatment modalities for leukemia.

Main Methods:

• Systematic review of current literature on leukemia immune microenvironment, epigenetics, and therapy.
• Analysis of epigenetic mechanisms (DNA methylation, histone modification, RNA modification) in leukemia immune evasion.
• Examination of combination therapy strategies involving epigenetic drugs, immune checkpoint inhibitors, BCL-2 inhibitors, and microenvironment-targeted agents.

Main Results:

• Leukemic cells manipulate the immune microenvironment to create a protective niche, promoting disease progression and resistance.
• Epigenetic alterations are crucial in mediating leukemia's immune evasion and influencing immunotherapy outcomes.
• Combination therapies integrating epigenetic drugs with immunotherapies and targeted agents show promise but face challenges.

Conclusions:

• Understanding immune microenvironment remodeling and epigenetic regulation is key to addressing leukemia drug resistance and relapse.
• Optimizing combination therapy strategies requires further research into microenvironment subtyping and precision interventions.
• Single-cell and spatial multi-omics technologies offer future directions for personalized leukemia treatment strategies.