Frontiers in Oncology (Jun 2021)
Intratumor Heterogeneity of MIF Expression Correlates With Extramedullary Involvement of Multiple Myeloma
- Juan Xu,
- Nanhui Yu,
- Nanhui Yu,
- Pan Zhao,
- Fangfang Wang,
- Jingcao Huang,
- Yushan Cui,
- Hong Ding,
- Yan Yang,
- Yuhan Gao,
- Ling Pan,
- Hong Chang,
- Yu Wu,
- Bing Xiang,
- Yuping Gong,
- Xiao Shuai,
- Li Hou,
- Liping Xie,
- Ting Niu,
- Ting Liu,
- Li Zhang,
- Weiping Liu,
- Wenyan Zhang,
- Ying Qu,
- Wei Lin,
- Wei Lin,
- Yimin Zhu,
- Sha Zhao,
- Yuhuan Zheng
Affiliations
- Juan Xu
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Nanhui Yu
- Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, China
- Nanhui Yu
- Hunan Provincial Key Lab of Emergency and Critical Care, Hunan Provincial People’s Hospital, Changsha, China
- Pan Zhao
- Department of Hematology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Fangfang Wang
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Jingcao Huang
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Yushan Cui
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Hong Ding
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Yan Yang
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Yuhan Gao
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Ling Pan
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Hong Chang
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Yu Wu
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Bing Xiang
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Yuping Gong
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Xiao Shuai
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Li Hou
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Liping Xie
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Ting Niu
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Ting Liu
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Li Zhang
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Weiping Liu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
- Wenyan Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
- Ying Qu
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Wei Lin
- Hunan Provincial Key Lab of Emergency and Critical Care, Hunan Provincial People’s Hospital, Changsha, China
- Wei Lin
- State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, China
- Yimin Zhu
- Hunan Provincial Key Lab of Emergency and Critical Care, Hunan Provincial People’s Hospital, Changsha, China
- Sha Zhao
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
- Yuhuan Zheng
- Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
- DOI
- https://doi.org/10.3389/fonc.2021.694331
- Journal volume & issue
-
Vol. 11
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.
Keywords
- extramedullary multiple myeloma
- MIF
- immunohistochemistry staining
- xenograft models
- single-cell sequencing
