Targeting vasculogenesis to prevent progression in multiple myeloma.

Area of Science:

• Hematology
• Oncology
• Vascular Biology

Background:

• The role of endothelial progenitor cells (EPCs) in hematological malignancies, particularly multiple myeloma (MM), remains underexplored.
• EPCs are crucial for vasculogenesis, the formation of new blood vessels from progenitor cells.

Purpose of the Study:

• To investigate the role of EPC-mediated vasculogenesis in the early stages of multiple myeloma (MM) progression.
• To determine the therapeutic potential of targeting EPCs and vasculogenesis in MM.

Main Methods:

• Mobilization and recruitment of EPCs in MM models were analyzed.
• EPC-defective mice (ID1+/- ID3-/-) were used to assess MM tumor progression.
• RNA sequencing was performed on MM cells and endothelial cells.
• A VEGFR2 antibody with anti-vasculogenic activity was employed to target EPCs.

Main Results:

• EPCs are mobilized from bone marrow to peripheral blood and recruit to MM niches early in disease.
• MM progression is dependent on EPC trafficking, with endothelial cells promoting proliferation in early-stage MM.
• Angiogenic dependency occurs early in MM progression.
• Early targeting of EPCs with a VEGFR2 antibody delays MM progression, while late-stage treatment is ineffective.

Conclusions:

• EPCs and early vasculogenesis are critical for the initiation and progression of multiple myeloma.
• Targeting EPC-mediated vasculogenesis at early disease stages shows therapeutic promise for MM.
• Early intervention in vasculogenesis could be a viable strategy for clinical trials in smoldering MM and precursor hematological conditions.