PB0779 - Low expression of coagulation inhibitors in the immune microenvironment in precursor stages of multiple myeloma

Background: High risk of venous thromboembolism has been observed among patients with a pre-neoplastic phase of multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), which indicates that the procoagulant state exists already before the onset of MM. Moreover, the expression of tissue factor, which is the initiator of coagulation and a key molecule in cancer-associated thrombosis, is absent in MM cells. Altogether, this indicates that other aberrant microenvironmental cells than MM cells alone are the main trigger for MM-associated thrombosis. Microenvironmental cells in the bone marrow (BM) play an important supportive role in regulating the pathological progression of MM. However, the role of microenvironmental cells in thrombogenesis of MM has not been explored.

Aims: To explore the potential involvement of BM microenvironmental cells in the thrombogenicity in precursor stages of MM.

Methods: The single-cell sequencing data from Zavidij et al. (Nat Cancer, 2020) was reused. By utilizing Seurat software, we explored and compared the expression level of coagulation-related factors in the CD45+ cells from the BM of patients with MGUS, smouldering MM (SMM), and MM as well as healthy controls.

Results: At single-cell resolution, we found that the mRNA expression of tissue factor pathway inhibitor (TFPI) and thrombomodulin was significantly decreased in the CD45+ microenvironmental cells in the BM of MGUS, SMM and MM compared to normal BM. No difference was found between MGUS, SMM and MM. Tissue factor (TF) expression was undetectable in the dataset. Factor V expression was repressed only in SMM.

Conclusion(s): Coagulation inhibitors were transcriptionally repressed in the BM microenvironment in the very early stages of MM, which is consistent with the high risk of thrombosis observed in patients with MGUS. We suggest that procoagulant BM microenvironment could underlie the thrombogenesis in the early stages of MM.