Transmissible ER stress reconfigures the AML bone marrow compartment

Area of Science:

• Hematology
• Cell Biology
• Cancer Biology

Background:

• Leukemogenesis involves bone marrow (BM) niche adaptation.
• Cellular mechanisms of BM niche alteration in AML are not fully understood.

Purpose of the Study:

• To define the cellular mechanisms by which AML remodels the BM niche.
• To investigate the role of endoplasmic reticulum (ER) stress and extracellular vesicles (EVs) in AML-induced BM alterations.

Main Methods:

• Utilized an AML xenograft model to study BM microenvironment changes.
• Analyzed ER stress and unfolded protein response (UPR) in leukemia and stromal cells.
• Investigated the role of extracellular vesicles (EVs) in transmitting ER stress and BMP2.
• Examined osteolineage differentiation of mesenchymal stem cells (MSCs).
• Corroborated findings in AML patient samples.

Main Results:

• AML incursion causes compartmental ER stress and UPR in leukemia and stromal cells.
• Extracellular vesicles (EVs) transmit ER stress from AML xenografts to BM stroma in vivo.
• UPR activation drives osteolineage differentiation of mesenchymal stem cells (MSCs).
• AML-EVs mediate the transfer of Bone Morphogenic Protein 2 (BMP2), a key osteogenic signal.
• AML-EVs function as a platform for BMP trafficking and intercellular communication.

Conclusions:

• AML-EVs play a critical role in remodeling the BM niche by transmitting ER stress and BMP2.
• This process promotes osteolineage differentiation and alters the BM microenvironment in AML.
• Findings highlight the translational relevance of AML-EVs in BMP trafficking and compartmental crosstalk.