BCL2 translocation frequency rises with age in humans
Open accessAbstract
The background frequency of t(14;18) (q32;q21) chromosomal translocations at the locus associated with B-cell leukemia/lymphoma-2 (BCL2) was determined from a survey of the peripheral blood lymphocytes (PBLs) of 53 living individuals and from tissues of 31 autopsies by using a nested PCR assay. The translocation was detected in 55% of PBLs and 35% of autopsied spleens with a frequency of between less than 1 to 853 translocations per million cells. Translocations copurified with B lymphocytes. The frequency of translocations significantly increased with age in PBLs and spleens, as does human risk for lymphoma. Average translocation frequency was more than 40 times greater in the spleen and 13 times greater in the peripheral blood in the oldest individuals (61 yr and older) compared with the youngest individuals (20 yr or younger). Particular t(14;18)-bearing clones persisted over a period of 5 months in two individuals. These findings demonstrate that clones harboring the oncogenic t(14;18) chromosomal translocation are commonly present in normal humans, that such clones are long-lived, and that they rise in frequency with age. A multihit model of lymphomagenesis involving t(14;18) translocation followed by antigen stimulation is proposed.
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Previously described mutations in the blood of healthy persons such as BCR-ABL or BCL2 translocations were usually present in less than 0.01% of cells and were often transient.
“For comparison, previously described mutations in the blood of healthy persons such as BCR-ABL or BCL2 translocations were usually present in less than 0.01% of cells and were often transient 29,30.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [30]
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- Authors
- Liu, Y., Hernandez, A. M., Shibata, D., & Cortopassi, G. A.
- Affiliations
- University of Southern California (US)
- ORCID
- Shibata, D
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-09-13
- Volume
- 91
- Issue
- 19
- Pages
- 8910-8914
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44716
- OpenAlex
- W2025635508
- Cited by
- 358
- References
- 35
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 11 · 2012: 9
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institutes of Health (5r01ca056407-03)
- National Institute on Aging (AG11967-01, R01AG011967)
- National Cancer Institute (CA56407-1)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- Bcl-2, aging, lymphoma risk, peripheral blood lymphocytes, spleen, B cells, clonal persistence, antigen stimulation, oncogenic translocation
- MeSH terms
- Adult, Aged, Aging, B-Lymphocytes, Base Sequence, Cell Survival, Child, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 18, Female, Fetus, Humans, Lymphoma, Male, Middle Aged, Molecular Sequence Data, Oncogenes, Proto-Oncogene Proteins, Spleen, Translocation, Genetic, DNA Primers, Proto-Oncogene Proteins c-bcl-2
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