AI Article Synopsis
- Immunoglobulin M (IgM) multiple myeloma (MM) is a rare condition that needs to be differentiated from other similar diseases, such as Waldenström macroglobulinemia, for effective treatment.
- The study involved analyzing genomic and transcriptomic data of IgM-MM samples through whole-genome and transcriptome sequencing, revealing shared characteristics with MM, but unique features like specific chromosomal translocations and deletions.
- Findings indicated that IgM-MM likely originates before the germinal center stage, highlighted by unique molecular signatures and elevated expression of potential therapeutic targets, such as CD20 and Bruton tyrosine kinase.
Article Abstract
Immunoglobulin M (IgM) multiple myeloma (MM) is a rare disease subgroup. Its differentiation from other IgM-producing gammopathies such as Waldenström macroglobulinemia (WM) has not been well characterized but is essential for proper risk assessment and treatment. In this study, we investigated genomic and transcriptomic characteristics of IgM-MM samples using whole-genome and transcriptome sequencing to identify differentiating characteristics from non-IgM-MM and WM. Our results suggest that IgM-MM shares most of its defining structural variants and gene-expression profiling with MM, but has some key characteristics, including t(11;14) translocation, chromosome 6 and 13 deletion as well as distinct molecular and transcription-factor signatures. Furthermore, IgM-MM translocations were predominantly characterized by VHDHJH recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints; coupled with its lack of class switching, these data favor a pre-germinal center origin. Finally, we found elevated expression of clinically relevant targets, including CD20 and Bruton tyrosine kinase, as well as high BCL2/BCL2L1 ratio in IgM-MM, providing potential for targeted therapeutics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602933 | PMC |
| http://dx.doi.org/10.1182/blood.2021011452 | DOI Listing |
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