Bone marrow mesenchymal stem cells are abnormal in multiple myeloma

Area of Science:

• Oncology
• Hematology
• Cell Biology

Background:

• Tumor microenvironment cells can exhibit abnormalities.
• Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow.

Purpose of the Study:

• To investigate the abnormalities of bone marrow mesenchymal stem cells (BMMSCs) in multiple myeloma (MM).
• To determine if MM BMMSCs contribute to the tumor microenvironment's supportive role.

Main Methods:

• Gene expression profiling of BMMSCs from MM patients, monoclonal gammopathy of undetermined significance (MGUS) patients, and healthy controls.
• Phenotypic and functional studies of BMMSCs.
• Analysis of differentially expressed genes and soluble factors.

Main Results:

• Gene expression profiling classified BMMSCs into normal and MM groups, with MGUS BMMSCs intermediate.
• Identified 145 differentially expressed genes in MM BMMSCs, with 46% potentially involved in tumor-microenvironment crosstalk.
• Discovered known (IL-6, DKK1) and novel soluble factors, including GDF15, which promotes myeloma cell growth.
• MM BMMSCs exhibited impaired osteoblastic differentiation and supported myeloma cell overgrowth.

Conclusions:

• Bone marrow mesenchymal stem cells (BMMSCs) are abnormal in multiple myeloma (MM) patients.
• Abnormal MM BMMSCs create a supportive niche that enhances myeloma cell survival and proliferation.
• These findings highlight the critical role of the tumor microenvironment in MM pathogenesis.