Zhong Ling/Yang Zhenglin Reveals Tumor Heterogeneity Between Different R-ISS Stages in Multiple Myeloma Patients Using Single-Cell Transcriptomics

The R-ISS (The Revised International Staging System) stratification system is a simple, reliable and widely used prognostic stratification system for multiple myeloma
.

Myeloma patients with different R-ISS stages presented significantly different prognosis
.

However, the reasons and regulatory networks that cause the significant prognostic differences between different R-ISS stages have not been elucidated, especially to explore the tumor heterogeneity at the single-cell transcriptome level
.

Recently, Yang Zhenglin's research group from Sichuan Provincial People's Hospital published a research paper entitled "Exploring the R-ISS stage-specific regular networks in the progression of Multiple Myeloma at single-cell resolution" in Science China Life Sciences, revealing that multiple myeloma Heterogeneity of tumor regulatory networks between different stages of R-ISS in tumor patients
.

Professor Yang Zhenglin's research group collected bone marrow samples from patients with different R-ISS stages and found that plasma cells were divided into 9 subgroups (P1-P9) at the single-cell transcriptome level, and the 5 subgroups P1-P5 were mainly concentrated in R-ISS stage III patients.
in
.

Among them, PDIA6 was significantly enriched in the P3 subgroup, and LETM1 was significantly enriched in the P1 subgroup
.

Both myeloma cell lines and myeloma cells isolated from clinical patients were used to verify that the two were significantly overexpressed in MM patients, especially in stage III patients
.

In this study, it was further found that PDIA6 may be activated by UQCRB and participate in the occurrence and development of MM through the oxidative phosphorylation pathway; LETM1 may be regulated by STAT1 to accelerate the process of MM through the C-type lectin pathway
.

The above regulatory network was verified by RNA interference experiments and cell proliferation ability experiments
.

Meanwhile, a subset of monocytes (M4) was only enriched in R-ISS stage III, and this subset specifically expressed the cytokines CCL3, CCL5, and CCL3L1
.

These cytokines act as ligand receptors that are only significantly active in phase III by binding to the CCR1 receptor on myeloma cells
.

Figure 1.
Single-cell transcriptional profiles and CNV profiles of bone marrow cells from patients with multiple myeloma
.

Figure 2.
Differential gene expression patterns in R-ISS stage progression in patients with multiple myeloma
.

Figure 3.
Mining of unique transcription factor motifs in R-ISS phase III by SCENIC analysis
.

Figure 4.
Analysis of differential expression of genes in monocytes in different R-ISS stages
.

Figure 5.
Predicted interactions between plasma cells and monocytes at different R-ISS stages
.

This study explored the molecular markers, regulatory networks, and dialogue patterns that were specifically enriched in multiple myeloma patients in different R-ISS stages, laying the foundation for a deep understanding of tumor heterogeneity and precise treatment of multiple myeloma
.

Dr.
Zhong Ling, Dr.
Yang Xiao, Dr.
Zhou Yu, and Master Xiao Jialing from Sichuan Provincial People's Hospital are the first authors of this article, and Professor Gong Bo and Professor Yang Zhenglin are the corresponding authors
.

For details of the research, please read the original text▼[Click the link below or read the original text]Zhong, L.
, Yang, X.
, Zhou, Y.
, Xiao, J.
, Li, H.
, Tao, J.
, Xi, Q.
, Chu, C.
, Li, C.
, Yang, X.
, et al.
(2022).
Exploring the R-ISS stage-specific regular networks in the progression of multiple myeloma at single-cell resolution.
Sci China Life Sci 65, https://doi.
org/10.
1007/s11427-021-2097-1