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Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression
Sabina Sevcikova1,2, Helena Paszekova3, Lenka Besse1,2
1Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Background:
Multiple myeloma (MM) is characterized by malignant proliferation of plasma cells (PC) which accumulate in the bone marrow (BM). The advent of new drugs has changed the course of the disease from incurable to treatable, but most patients eventually relapse. One group of MM patients (10-15%) is considered high-risk because they relapse within 24 months. Recently, extramedullary relapse of MM (EM) has been observed more frequently. Due to its aggressivity and shorter survival, EM is also considered high-risk.
Aims:
The goal of this study was to determine if the so-called high-risk genes published by the University of Arkansas group (UAMS) are even more deregulated in EM patients than in high-risk MM patients and if these patients may be considered high-risk.
Methods:
Nine samples of bone marrow plasma cells from MM patients as well as 9 tumors and 9 bone marrow plasma cells from EM patients were used. Quantitative real-time PCR was used for evaluation of expression of 15 genes connected to the high-risk signature of MM patients.
Results:
Comparison of high-risk plasma cells vs extramedullary plasma cells revealed 4 significantly deregulated genes (CKS1B, CTBS, NADK, YWHAZ); moreover, comparison of extramedullary plasma cells vs extramedullary tumors revealed significant differences in 9 out of 15 genes. Of these, 6 showed significant changes as described by the UAMS group (ASPM, SLC19A1, NADK, TBRG4, TMPO and LARS2).
Conclusions:
Our data suggest that increasing genetic abnormalities as described by the gene expression data are associated with increased risk for EM relapse.
Insights
Extramedullary relapse (EM) in multiple myeloma (MM) shows increased genetic abnormalities compared to high-risk MM. These findings suggest EM patients may represent a higher-risk group requiring closer monitoring.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Multiple myeloma (MM) is a plasma cell malignancy in bone marrow.
- While new treatments improve outcomes, most patients relapse, with 10-15% classified as high-risk.
- Extramedullary relapse (EM) is increasingly recognized as an aggressive, high-risk form of MM.
Purpose of the Study:
- To investigate if high-risk genes are more deregulated in EM patients than in high-risk MM patients.
- To assess if EM patients can be classified as a distinct high-risk group based on gene expression.
Main Methods:
- Analysis of 15 high-risk signature genes using quantitative real-time PCR.
- Comparison of gene expression in bone marrow plasma cells from MM patients versus plasma cells and tumors from EM patients.
Main Results:
- Four genes (CKS1B, CTBS, NADK, YWHAZ) were significantly deregulated in high-risk plasma cells versus extramedullary plasma cells.
- Nine out of 15 genes showed significant differences between extramedullary plasma cells and tumors, with 6 matching the UAMS high-risk signature.
Conclusions:
- Gene expression data indicates increasing genetic abnormalities are linked to higher risk of EM relapse.
- This suggests a potential molecular basis for classifying EM patients as a high-risk group.
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