Project description:Multiple myeloma is a plasma cell malignancy characterized by the abnormal increase of monoclonal immunoglobulins. Despite great treatment advances, there are still patients experiencing migration of tumor cells from the bone marrow and progression of the disease into its aggressive forms including extramedullary disease or plasma cell leukemia. Although the exact molecular mechanisms are not known, several studies have confirmed the involvement of small extracellular vesicles-enriched microRNAs in multiple myeloma progression. Thus, we have performed the expression profiling of these molecules in bone marrow plasma of patients with multiple myeloma, extramedullary disease, and plasma cell leukemia using next-generation sequencing with the aim to identify new molecules involved in the disease pathogenesis. In total, 42 microRNAs were wound to be significantly deregulated among analyzed subgroups. The independent validation by RT-qPCR confirmed the elevated levels of miR-140-3p, miR-584-5p, miR-191-5p, and miR-143-3p in patients with multiple myeloma compared to extramedullary disease and/or plasma cell leukemia. Subsequent statistical analysis proved several significant correlations between clinical characteristics or flow cytometry parameters of patients and microRNAs’ expression. In addition, low levels of miR 140 3p, miR-191-5p, miR-744-5p, and miR-143-3p were associated with worse overall survival. These results indicate that deregulation of microRNAs could contribute to multiple myeloma progression. Nevertheless, the exact mechanisms have yet to be clarified.
Project description:A patient derived orthotopic xenograft (PDOX) was generated from a patient with an 53 aggressive extramedullary multiple myeloma (EMM) to study in-depth genetic and epigenetic events and drug responses related to extramedullary disease. Whole DNA methylome of the EMM PDOX was also evaluated and compared with a published dataset of 101 newly-diagnosed and chemotherapy-naïve MM patients and normal plasma cells (NPC) (Agirre et al., 2015) A rather balanced proportion of hyper/hypomethylated sites different to previously reported widespread hypomethylation in MM was observed.
Project description:Despite the development of novel therapeutic agents, multiple myeloma (MM) remains incurable, owing mainly to inevitable relapse in almost all patients. Some relapses occur as extramedullary disease (EMD), which is rare but is the most aggressive event in MM patients. Extramedullary myeloma (EMM) has extraordinary heterogeneous biological and clinical features. Previous studies have shown that expression levels of LncRNAs and mRNAs in different stages of MM are different. This study analyzes the expression levels of LncRNAs and mRNAs in primary plasma cells (PCs) from MM and EMM patients.
Project description:Myelomatous effusion (ME) is a rare manifestion of extramedullary multiple myeloma (MM) with limited therapeutic options and poor outcomes. To investigate the evolutionary mechanisms of ME, we used single-cell RNA sequencing to assess the transcriptomes of bone marrow, peripheral blood, and pleural effusion/ascites from three patients with ME.
