AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation
Open accessAbstract
Leukemia-specific AML1/ETO transcripts are detectable in most patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. To understand the inconsistency between the clinical cure and the presence of "residual disease" at a molecular level, we separated and identified the cells expressing AML1/ETO by phenotype and function. Here we demonstrate that AML1/ETO transcripts are present in a fraction of stem cells, monocytes, and B cells in remission marrow, and in a fraction of B cells in leukemic marrow, but not in T cells. AML1/ETO transcripts also were demonstrated in a fraction of colony-forming cells of erythroid, granulocyte-macrophage, and/or megakaryocyte lineages in both leukemic and remission marrow. These data strongly suggest that the acquisition of the t(8;21) occurs at the level of stem cells capable of differentiating into B cells as well as all myeloid lineages, and that a fraction of the AML1/ETO-expressing stem cells undergo additional oncogenic event(s) that ultimately leads to transformation into AML.
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- Authors
- Miyamoto, T., Weissman, I. L., & Akashi, K.
- Affiliations
- Stanford Medicine (US)
- Dana-Farber Cancer Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-06-20
- Volume
- 97
- Issue
- 13
- Pages
- 7521-7526
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC16578
- OpenAlex
- W2097519948
- Cited by
- 465
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 10 · 2021: 15 · 2020: 9 · 2019: 16 · 2018: 8 · 2017: 20 · 2016: 17 · 2015: 31 · 2014: 26 · 2013: 17 · 2012: 24
- FWCI
- 11.95
- 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
- Uehara Memorial Foundation
- National Institutes of Health (5r35ca042551-13)
- U.S. Public Health Service
- National Cancer Institute (CA 42551)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- AML1-ETO, acute myeloid leukemia, leukemia stem cells, residual disease, B cells, monocytes, colony-forming cells, oncogenic transformation, leukemogenesis
- MeSH terms
- Adult, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 8, DNA-Binding Proteins, Female, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Proto-Oncogene Proteins, Transcription Factors, Translocation, Genetic, Leukemia, Myeloid, Acute, Neoplasm, Residual, Antigens, CD34, Core Binding Factor Alpha 2 Subunit
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