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Cited by 1,513Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationCancer Cells and Metastasis

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Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9

Krivtsov, Andrei V., Twomey, David, Feng, Zhaohui, Stubbs, Matthew C., Wang, Yingzi, Faber, Joerg, Levine, Jason E., Wang, Jing, Hahn, William C., Gilliland, D. Gary, Golub, Todd R., Armstrong, Scott A.·2006·Nature
DOI 10.1038/nature04980
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Abstract

Leukaemias and other cancers possess a rare population of cells capable of the limitless self-renewal necessary for cancer initiation and maintenance. Eradication of these cancer stem cells is probably a critical part of any successful anti-cancer therapy, and may explain why conventional cancer therapies are often effective in reducing tumour burden, but are only rarely curative. Given that both normal and cancer stem cells are capable of self-renewal, the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. However, it remains unclear whether cancer stem cells must be phenotypically similar to normal tissue stem cells or whether they can retain the identity of committed progenitors. Here we show that leukaemia stem cells (LSC) can maintain the global identity of the progenitor from which they arose while activating a limited stem-cell- or self-renewal-associated programme. We isolated LSC from leukaemias initiated in committed granulocyte macrophage progenitors through introduction of the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23). The LSC were capable of transferring leukaemia to secondary recipient mice when only four cells were transferred, and possessed an immunophenotype and global gene expression profile very similar to that of normal granulocyte macrophage progenitors. However, a subset of genes highly expressed in normal haematopoietic stem cells was re-activated in LSC. LSC ca…

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Metadata

Authors
Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W. C., Gilliland, D. G., Golub, T. R., & Armstrong, S. A.
Affiliations
  • Boston Children's Hospital (US)
  • Broad Institute (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Armstrong, Scott A.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2006-07-16
Volume
442
Issue
7104
Pages
818-822
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature04980
OpenAlex
W2109336877
Cited by
1,513
References
0
Citations by year
2026: 37 · 2025: 45 · 2024: 66 · 2023: 70 · 2022: 60 · 2021: 65 · 2020: 66 · 2019: 73 · 2018: 70 · 2017: 75 · 2016: 85 · 2015: 83 · 2014: 77 · 2013: 79 · 2012: 92
FWCI
59.70
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Damon Runyon Cancer Research Foundation
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
leukemia stem cells, committed progenitors, MLL-AF9 fusion, CFU-GM, self-renewal, cancer stem cells, hematopoietic stem cells, gene expression profiling, oncogenic transformation, targeted cancer therapy
MeSH terms
Animals, Cell Differentiation, Cell Division, Cell Line, Cell Transformation, Neoplastic, Granulocytes, Humans, Leukemia, Macrophages, Neoplasm Transplantation, Neoplastic Stem Cells, Leukemia, Myelomonocytic, Acute, Oncogene Proteins, Fusion, Survival Rate, Cell Lineage, Mice, Myeloid-Lymphoid Leukemia Protein

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