Abstract
Macrophage migration inhibitory factor (MIF) has been shown to promote disease progression in many malignancies, including multiple myeloma (MM). We previously reported that MIF regulates MM bone marrow homing and knockdown of MIF favors the extramedullary myeloma formation in mice. Here, based on MIF immunostaining of myeloma cells in paired intramedullary and extramedullary biopsies from 17 patients, we found lower MIF intensity in extramedullary MM (EMM) versus intramedullary MM (IMM). Flow cytometry and histology analysis in xenograft models showed a portion of inoculated human MM cells lost their MIF expression (MIFLow) in vivo. Of note, IMM had dominantly MIFHigh cells, while EMM showed a significantly increased ratio of MIFLow cells. Furthermore, we harvested the extramedullary human MM cells from a mouse and generated single-cell transcriptomic data. The developmental trajectories of MM cells from the MIFHigh to MIFLow state were indicated. The MIFHigh cells featured higher proliferation. The MIFLow ones were more quiescent and harbored abundant ribosomal protein genes. Our findings identified in vivo differential regulation of MIF expression in MM and suggested a potential pathogenic role of MIF in the extramedullary spread of disease.
Highlights
The proliferation of clonal plasma cells in multiple myeloma (MM) is typically confined to the bone marrow (BM)
Formalin-fixed, paraffin-embedded (FFPE) paired tumor samples of BM and extramedullary tissues were retrospectively collected from 17 MM patients who had extramedullary involvement with the following inclusion criteria: 1) the patient was admitted to our hospital from 2014 to 2019; 2) the patient with confirmed MM had pathologically verified extramedullary involvement either at initial diagnosis or during relapse/progression; 3) imaging or physical examination showed measurable lesions of extramedullary multiple myeloma (EMM)
Both EM-B and EM-E myeloma were included in this study; 4) EMM and the corresponding intramedullary MM (IMM) samples from each patient were collected at the same disease stage
Summary
The proliferation of clonal plasma cells in multiple myeloma (MM) is typically confined to the bone marrow (BM). The extramedullary spread of MM cells, defined as extramedullary multiple myeloma (EMM), may occur at any time in the course of MM [1]. Patients with EMM have inferior outcomes [2, 3]. Heterogenous MIF Expression in EMM local bone lesions (para-skeletal or extramedullary bone-related, EM-B) or resulting from hematogenous dissemination (extraskeletal or extramedullary-extraosseous, EM-E) [1, 4, 5]. Plasma cell leukemia (PCL) might be considered as a specific variant of EMM [5]. Some authors have suggested that PCL should be excluded from the EMM spectrum because of PCL’s unique disease entity [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
