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Patients with rapidly progressing multiple myeloma showed distinct overexpression of genetic markers related to cancer-facilitating cellular activity. This study sheds light on the variations in disease progression and paves the way for personalized treatment strategies.

  • Multiple myeloma is an aggressive cancer with a low survival rate.
  • Some patients experience more rapid disease progression than others.
  • Cancer cells from multiple myeloma patients had distinct genetic profiles

Multiple myeloma (MM) is a prevalent hematological cancer, making up 10% of all hematological malignancies in the United States. Despite therapeutic advances in immunomodulatory drugs, there is no cure for MM. Aggressive myeloma cell proliferation, treatment resistance, and immune evasion contribute to the short survival rate in MM patients.

Bone Marrow Microenvironment and Disease Progression

In the bone marrow microenvironment, where cancerous plasma cells originate, complex interactions of genes and epigenetics determine disease progression. Certain profiles of immune and stromal cells are associated with poorer prognosis. Enrichment of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, and scarcity of CD4+ or CD8+ T cells and natural killer cells create an immunosuppressive environment.

In patients with advanced disease, bone marrow T-cells show increased numbers of immune-inhibitory receptors and markers related to senescence compared to healthy controls. Characterizing immune profiles of bone marrow from patients with different rates of progression can identify markers of rapid disease progression and potential protective factors.

Single-Cell RNA-Sequencing in Rapid Progressors and Non-Progressors

In a cross-center study published in NPJ Genomic Medicine, single-cell RNA sequencing (scRNA-seq) was performed in 48 bone marrow biopsies from 18 patients. Patients were classified as “rapid progressors” if their progression-free survival (PFS) was less than 18 months, or “non-progressors” if their PFS was greater than four years. CD138 cell fractions identified as myeloma cancer cells from these patients comprised a dataset of over 100,000 single cells.

Across three medical centers in Boston, St. Louis, and New York, similar gene expression profiles were found, validating the use of multiple sites for the study. Patients who were rapid progressors had enriched CD8+ T cell exhaustion, with higher enrichment of metabolic pathways and decreased expression of cytolytic markers. M2 macrophages were enriched in rapid progressors, and they overexpressed genes facilitating proliferation pathways. Non-progressors were enriched in immature B cells and genes related to cytotoxicity and T-cell activation, potentially indicating better T-cell function.

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Identifying Biomarkers for Novel Therapies in Multiple Myeloma

This study lays the groundwork for developing an immune atlas of the tumor microenvironment. Identifying tumor-facilitating cell populations associated with rapid MM disease progression will contribute to development of novel biomarker-based therapies. 

Source: 

Pilcher, W., Thomas, B. E., Bhasin, S. S., Jayasinghe, R. G., Yao, L., Gonzalez-Kozlova, E., Dasari, S., Kim-Schulze, S., Rahman, A., Patton, J., Fiala, M., Cheloni, G., Kourelis, T., Dhodapkar, M. V., Vij, R., Mehr, S., Hamilton, M., Cho, H. J., Auclair, D., . . . Bhasin, M. (2023). Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma. NPJ Genom Med, 8(1), 3. https://doi.org/10.1038/s41525-022-00340-x