Inflammatory mechanisms in the AML bone marrow niche: From pathogenesis to therapy

Area of Science:

• Hematology
• Immunology
• Oncology

Background:

• Acute myeloid leukemia (AML) is characterized by dysregulated cytokine networks, favoring pro-inflammatory mediators over anti-inflammatory ones.
• This cytokine imbalance creates a pro-tumorigenic microenvironment, enhancing leukemic cell proliferation, survival, and drug resistance.
• Inflammatory cytokines also support mutated hematopoietic stem and progenitor cells, contributing to clonal hematopoiesis.

Purpose of the Study:

• To review the role of inflammatory cytokines and signaling pathways in AML pathogenesis.
• To explore the implications of these pathways in immune tolerance and clonal hematopoiesis.
• To summarize emerging therapeutic strategies targeting inflammatory pathways for AML treatment.

Main Methods:

• Literature review of current knowledge on inflammatory cytokines in AML.
• Analysis of cytokine network dysregulation and its impact on the tumor microenvironment.
• Examination of therapeutic strategies targeting inflammatory signaling in AML.

Main Results:

• Inflammatory cytokines like IL-1β, TNF-α, and IL-6 are elevated in AML, promoting leukemogenesis.
• Cytokine dysbalance contributes to immune evasion and supports the expansion of pre-leukemic clones.
• Targeting inflammatory pathways shows promise for novel AML therapies.

Conclusions:

• Inflammatory signaling is a critical driver of AML progression and therapeutic resistance.
• Understanding these pathways is key to developing effective treatments for AML.
• Targeted therapies offer a promising avenue to improve clinical outcomes in AML.