Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia
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Reduced lymphopoiesis during aging contributes to declines in immunity, but little consideration has been given to its effect on the development of hematologic disease. This report demonstrates that age-related defects in lymphopoiesis underlie the myeloid dominance of adult leukemia. Using a murine model of chronic myeloid leukemia, an adult-onset malignancy that arises from transformation of hematopoietic stem cells by the BCR-ABL(P210) oncogene, we demonstrate that young bone marrow (BM) cells that were transformed with BCR-ABL(P210) initiated both a myeloproliferative disorder (MPD) and B-lymphoid leukemia, whereas BCR-ABL(P210)-transformed old BM cells recapitulated the human disease by inducing an MPD with rare lymphoid involvement. In addition, the lesser severity of MPDs initiated from old BCR-ABL(P210)-transduced BM cells revealed unappreciated defects in aged myeloid progenitors. These data demonstrate that aging affects patterns of leukemogenesis and indicate that the effects of senescence on hematopoiesis are more extensive than previously appreciated.
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The same oncogenic mutation causes more aggressive disease in aged stem cells than in young cells.
“Also, there is some evidence (but not a lot) that the same oncogenic mutation results in a more aggressive disease in aged stem cells compared with young cells.105”
From Aging of hematopoietic stem cells (2018) · cites this paper as [105]
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- Authors
- Signer, R. A. J., Montecino-Rodriguez, E., Witte, O. N., McLaughlin, J., & Dorshkind, K.
- Affiliations
- UCLA Jonsson Comprehensive Cancer Center (US)
- Department of Pathology and Laboratory Medicine and the Hematopoietic Malignancies Program, Jonsson Comprehensive Cancer Center;
- Howard Hughes Medical Institute (US)
- Departments ofMicrobiology, Immunology and Molecular Genetics and
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-09-15
- Volume
- 110
- Issue
- 6
- Pages
- 1831-1839
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1976345
- OpenAlex
- W2076900669
- Cited by
- 77
- References
- 67
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-21459)
- National Cancer Institute (CA-16 042, P30CA016042)
- National Institute of Allergy and Infectious Diseases (P30AI028697)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- aging, B cell development, adult leukemia, chronic myeloid leukemia, BCR-ABL, hematopoietic stem cells, myeloproliferative neoplasms, hematologic malignancies, hematopoietic progenitor cells, senescence, lymphoid leukemia, bone marrow
- MeSH terms
- Adult, Aging, Animals, B-Lymphocytes, Disease Models, Animal, Flow Cytometry, Hematopoiesis, Hematopoietic Stem Cells, Humans, Leukemia, Lymphoid, Mice, Inbred C57BL, Myeloproliferative Disorders, Retroviridae, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Bone Marrow Transplantation, Fusion Proteins, bcr-abl, Immunophenotyping, Age of Onset, Homeodomain Proteins, Myeloid Cells, Lymphopoiesis, Mice
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