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 Geng^1,², Jing Wang¹, Changjian Yan¹, Xiannian Zhang^1,², Jia-jia Zhang³, Fan Wu^1,², Yuhong Pang^1,², Yuping Zhong³, Jianbin Wang⁴, Wei Fu¹, Xin Huang¹, Wenming Wang¹, Xiaoqing Lyu^1,², Yanyi Huang^1,², Hongmei Jing¹

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

* Equal contribution

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

https://doi.org/10.18632/aging.204697

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.

Abstract

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.