Bone Marrow Microenvironment Involvement in t-MN: Focus on Mesenchymal Stem Cells

Area of Science:

• Hematology
• Oncology
• Stem Cell Biology

Background:

• Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT).
• Historically, t-MN was attributed solely to DNA damage in hematopoietic stem/progenitor cells (HSPC).
• Emerging evidence implicates the bone marrow microenvironment (BMM), particularly bone marrow mesenchymal stem cells (BM-MSCs), in t-MN pathogenesis.

Purpose of the Study:

• To review the role of BM-MSCs in the pathogenesis of therapy-related myeloid neoplasms (t-MN).
• To explore how CT affects BM-MSC function and contributes to malignant hematopoiesis.
• To summarize observed alterations in BM-MSCs from t-MN patients.

Main Methods:

• Literature review focusing on the role of BM-MSCs in t-MN.
• Analysis of studies investigating BM-MSC function in the context of cytotoxic therapy.
• Comparison of BM-MSC characteristics in t-MN patients versus healthy controls.

Main Results:

• Chemo/radiotherapy can damage BM-MSCs, altering their function and promoting inflammation and malignant hematopoiesis.
• BM-MSCs from t-MN patients exhibit reduced proliferation, altered morphology, increased senescence, and impaired support for HSCs.
• Defective osteogenic differentiation and immune-regulatory properties are observed in t-MN-associated BM-MSCs.

Conclusions:

• BM-MSCs are critical players in t-MN pathogenesis, contributing beyond direct DNA damage to HSPCs.
• Dysfunctional BM-MSCs create a pro-malignant microenvironment, favoring the development of t-MN.
• Further research into the genetic and functional profiles of t-MN-MSCs is crucial for prognostic and therapeutic advancements.