Bone marrow niches in haematological malignancies

Area of Science:

• Hematology
• Cancer Biology
• Stem Cell Biology

Background:

• Hematological malignancies were traditionally attributed solely to genetic/epigenetic changes in blood cells.
• The bone marrow microenvironment (niche) is increasingly recognized for its critical role in blood cell development and disease.
• Niche alterations can predispose to, facilitate, and drive the progression of blood cancers.

Purpose of the Study:

• To review the current understanding of bone marrow niche composition and function in health and disease.
• To explore shared niche-associated disease mechanisms across various hematological malignancies.
• To highlight the role of niches in chemoresistance and relapse.

Main Methods:

• Review of existing literature on bone marrow niche biology and hematological malignancies.
• Discussion of disease mechanisms focusing on niche alterations rather than specific cancer subtypes.
• Analysis of pathways including niche cell mutations, hypoxia, angiogenesis, inflammation, and metabolic reprogramming.

Main Results:

• Bone marrow niche alterations contribute significantly to the initiation, progression, and chemoresistance of hematological malignancies.
• Key niche-associated mechanisms include mutations in niche cells, hypoxia, angiogenesis, inflammation, and metabolic changes.
• Niche remodeling promotes immune evasion, survival pathways, and protection from chemotherapy, leading to relapse.

Conclusions:

• Integrating knowledge of bone marrow niche contributions into clinical practice is crucial for improving hematological malignancy treatment.
• Understanding niche-driven mechanisms can identify novel therapeutic targets.
• Guidelines for sample handling and niche analysis are proposed to facilitate clinical translation.