AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center Malignancies
Open accessAbstract
By misdirecting the activity of Activation-Induced Deaminase (AID) to a conditional MYC transgene, we have achieved sporadic, AID-dependent MYC activation in germinal center B cells of Vk*MYC mice. Whereas control C57BL/6 mice develop benign monoclonal gammopathy with age, all Vk*MYC mice progress to an indolent multiple myeloma associated with the biological and clinical features highly characteristic of the human disease. Furthermore, antigen-dependent myeloma could be induced by immunization with a T-dependent antigen. Consistent with these findings in mice, more frequent MYC rearrangements, elevated levels of MYC mRNA, and MYC target genes distinguish human patients with multiple myeloma from individuals with monoclonal gammopathy, implicating a causal role for MYC in the progression of monoclonal gammopathy to multiple myeloma.
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The B-cells from which multiple myeloma originates experience prolonged or chronic stimulation in the germinal center.
“In fact, several studies have supported the idea that the B-cells from which MM originate, experience a prolonged/chronic stimulation in the GC.15,40,41,70,71”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [70]
The Discussion (page unavailable) says chronic antigenic stimulation has long been implicated in MM development, and the paper reports MYC activation in germinal-center B cells in its mouse model. It does not establish that the B cells giving rise to MM undergo prolonged stimulation specifically within the germinal center. (LLM, conf=0.83)
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Prevalence of monoclonal gammopathy of undetermined significance
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Research works printed but not linked: 10
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Evolution of Multiple Myeloma from a Genomic Perspective
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- Authors
- Chesi, M., Robbiani, D. F., Sebag, M., Chng, W. J., Affer, M., Tiedemann, R., Valdez, R., Palmer, S. E., Haas, S. S., Stewart, A. K., Fonseca, R., Kremer, R., Cattoretti, G., & Bergsagel, P. L.
- Affiliations
- Mayo Clinic in Arizona (US)
- Cornell University (US)
- McGill University Health Centre (CA)
- University of Milano-Bicocca (IT)
- Corresponding author
- Chesi, Marta
- Bergsagel, P. Leif
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 13
- Issue
- 2
- Pages
- 167-180
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2255064
- OpenAlex
- W2012182672
- Cited by
- 393
- References
- 2
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 29 · 2023: 20 · 2022: 22 · 2021: 31 · 2020: 26 · 2019: 22 · 2018: 28 · 2017: 19 · 2016: 19 · 2015: 23 · 2014: 24 · 2013: 27 · 2012: 24
- FWCI
- 12.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2029 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- National Institutes of Health (P01-CA62242, P50-CA100707, RO1-AG020686, RO1-CA129009, RO1-CA83724)
- Multiple Myeloma Research Foundation
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- activation-induced cytidine deaminase, c-Myc, multiple myeloma, monoclonal gammopathy, germinal center B cells, T-dependent antigens, MYC rearrangement, B-cell malignancies, mouse model
- MeSH terms
- AICDA (Activation-Induced Cytidine Deaminase), Animals, Antigens, Neoplasm, Cytidine Deaminase, Disease Models, Animal, DNA Mutational Analysis, Drug Screening Assays, Antitumor, Humans, Immunization, Models, Biological, Molecular Sequence Data, Multiple Myeloma, Organ Specificity, Paraproteinemias, Plasma Cells, Protein Engineering, Proto-Oncogene Proteins c-myc, Codon, Terminator, Disease Progression, Germinal Center, Transgenes, Gene Expression Profiling, Somatic Hypermutation, Immunoglobulin, Cell Proliferation, Mice
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