IgM-MM is predominantly a pre–germinal center disorder and has a distinct genomic and transcriptomic signature from WM
Open accessAbstract
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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Rare IgM-MM lacks class switching.
“coupled with its lack of class switching, these data favor a rare pre-GC origin.66”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [66]
The Driver mutations section reports that most IgM-MM samples (73%) lacked the class-switch deletions seen in IgG/IgA-MM. It also says four samples appeared to have fully class switched, although their cells exclusively produced IgM. Thus, lack of class switching is supported as a predominant pattern, not an absolute one. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe VHDHJH breakpoints and lack of class switching in rare IgM-MM favor a rare pre-germinal-center origin.
“coupled with its lack of class switching, these data favor a rare pre-GC origin.66”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [66]
In rare IgM-MM, IgH translocations are predominantly characterized by VHDHJH recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints.
“In rare cases of IgM-MM, IgH translocations are predominantly characterized by VHDHJH recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints;”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [66]
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Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003 · see citing works
The generation of antibody-secreting plasma cells
Nutt, S. L., Hodgkin, P. D., Tarlinton, D. M., & Corcoran, L. M. (2015) · Nature reviews. Immunology · doi:10.1038/nri3795 · Cited by 1,446 · see citing works
The molecular classification of multiple myeloma
Zhan, F., Huang, Y., Colla, S., Stewart, P., Hanamura, I., Gupta, S. K., Epstein, J., Yaccoby, S., Sawyer, J. R., Burington, B. E., et al. (2006) · Blood · doi:10.1182/blood-2005-11-013458 · Cited by 1,137 · see citing works
Regulation of plasma-cell development
Shelef, M. A., & Calame, K. L. (2005) · Nature reviews. Immunology · doi:10.1038/nri1572 · Cited by 881 · see citing works
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Bolli, N., Avet-Loiseau, H., Wedge, D. C., Van Loo, P., Alexandrov, L. B., Martincorena, I., Dawson, K. J., Iorio, F., Nik-Zainal, S., Bignell, G. R., et al. (2014) · Nature Communications · doi:10.1038/ncomms3997 · Cited by 875 · see citing works
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Hunter, Z. R., Xu, L., Yang, G., Zhou, Y., Liu, X., Cao, Y., Manning, R. J., Tripsas, C. K., Patterson, C. J., Sheehy, P. S., et al. (2013) · Blood · doi:10.1182/blood-2013-09-525808 · Cited by 484 · see citing works
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Walker, B. A., Mavrommatis, K., Wardell, C. P., Ashby, T. C., Bauer, M., Davies, F. E., Rosenthal, A., Wang, H., Qu, P., Hoering, A., et al. (2018) · Blood · doi:10.1182/blood-2018-03-840132 · Cited by 475 · see citing works
Self-citationKumar, S. K., Harrison, S. J., Cavo, M., de la Rubia, J., Popat, R., Gasparetto, C., Hungria, V., Salwender, H. J., Suzuki, K., Kim, I., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30525-8 · Cited by 404 · see citing works
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Self-citationPunnoose, E. A., Leverson, J. D., Peale, F. V., Jr., Boghaert, E. R., Belmont, L. D., Tan, N., Young, A., Mitten, M. J., Ingalla, E., Darbonne, W. C., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0730 · Cited by 307 · see citing works
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Braggio, E., Doǧan, A., Keats, J. J., Chng, W. J., Huang, G., Matthews, J. M., Maurer, M. J., Law, M. E., Bosler, D. S., Barrett, M. T., et al. (2012) · Modern Pathology · doi:10.1038/modpathol.2011.213 · Cited by 69 · see citing works
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Research works printed but not linked: 1
- M.K.S., 0000-0002-9978-5682. Correspondence: Mehmet Kemal Samur, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, 450 Brookline Ave, Boston, MA 02215; e-mail: mehmet_samur@dfci.harvard.edu; and Nikhil C. Munshi, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215; e-mail: nikhil_munshi@dfci.harvard. edu. Footnotes Submitted 28 February 2021; accepted 18 August 2021; prepublished online on Blood First Edition 31 August 2021. DOI 10.1182/ blood.2021011452.
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- Authors
- Bazarbachi, A. H., Avet-Loiseau, H., Szalat, R., Samur, A. A., Hunter, Z., Shammas, M., Corre, J., Fulciniti, M., Anderson, K. C., Parmigiani, G., Treon, S. P., Mohty, M., Munshi, N. C., & Samur, M. K.
- Affiliations
- Albert Einstein College of Medicine (US)
- University Cancer Center of Toulouse, Institut National de la Santé, Toulouse, France;
- Boston University (US)
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA;
- Harvard University (US)
- Inserm (FR)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2021-11-18
- Volume
- 138
- Issue
- 20
- Pages
- 1980-1985
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC8602933
- OpenAlex
- W3196948396
- Cited by
- 21
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 1
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX001584)
- National Institutes of Health (CA100707)
- National Cancer Institute (P50CA100707, P01CA155258, CA100707)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- Waldenström macroglobulinemia, structural variants, gene expression profiling, CD20, Bruton's tyrosine kinase, targeted therapy
- MeSH terms
- Humans, Immunoglobulin M, Waldenstrom Macroglobulinemia, Multiple Myeloma, Mutation, Translocation, Genetic, Germinal Center, DNA Copy Number Variations, Transcriptome
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