Research Paper Volume 15, Issue 9 pp 3644—3677

FAM46C-mediated tumor heterogeneity predicts extramedullary metastasis and poorer survival in multiple myeloma

Weilong Zhang1, *, , Chaoling Wu1, *, , Shuang Geng1,2, *, , Jing Wang1, *, , Changjian Yan1, , Xiannian Zhang1,2, , Jia-jia Zhang3, , Fan Wu1,2, , Yuhong Pang1,2, , Yuping Zhong3, , Jianbin Wang4, , Wei Fu1, , Xin Huang1, , Wenming Wang1, , Xiaoqing Lyu1,2, , Yanyi Huang1,2, , Hongmei Jing1, ,

  • 1 Department of Hematology, Biodynamic Optical Imaging Center (BIOPIC) and Lymphoma Research Center, Third Hospital, Peking University, Beijing 100084, China
  • 2 Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100084, China
  • 3 Department of Hematology, Beijing Chaoyang Hospital West, Capital Medical University, Beijing 100054, China
  • 4 School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100190, China
* Equal contribution

Received: March 22, 2019       Accepted: April 22, 2023       Published: May 6, 2023
How to Cite

Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Cancers originate from a single cell according to Nowell’s theory of clonal evolution. The enrichment of the most aggressive clones has been developed and the heterogeneity arises for genomic instability and environmental selection. Multiple myeloma (MM) is a multiple relapse plasma cell cancer generated from bone marrow. Although there were accumulating researches in multiple myeloma pathogenesis, the heterogeneity remains poorly understood. The participants enrolled in this study were 4 EMP+ (EMP, Extramedullary plasmacytoma) and 2 EMP- primarily untreated MM patients. Single cell RNA sequencing and analysis were conducted for the single cell suspension, which was sorted by flow cytometry from peripheral blood mononuclear cells or bone marrow cells. In our research, the results of single cell RNA sequencing show that FAM46C determines MM tumor heterogeneity predicting extramedullary metastasis by influencing RNA stability. Further, we integrated and analyzed 2280 multiple myeloma samples from 7 independent datasets, which uncover that FAM46C mediated tumor heterogeneity predicts poorer survival in multiple myeloma.


ASCT: autologous stem cell transplantation; BM: bone marrow; BMCs: bone marrow cells; BMMC: myeloma cells in bone marrow; CPCs: clonal circulating plasma cells; DEG: different expressed genes; Dex: dexamethasone; EMP: Extramedullary plasmacytoma; FC: foldchange; Ig: immunoglobulin; IMWG: the International Myeloma Working Group; ISS: the international staging system; LDH: lactate dehydrogenase; MM: Multiple myeloma; OS: overall survival; PBMCs: peripheral blood mononuclear cells; R-ISS: revised International Classification System; TT2: autologous hematopoietic stem-cell transplantation and thalidomide therapy; TT3: incorporating bortezomib up-front into a tandem transplant regimen; VAD: Vincristine, Adriamycin, and Dexamethasone.