Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b
Open accessAbstract
Hoxa9, Meis1 and Pbx1 encode homeodomaincontaining proteins implicated in leukemic transformation in both mice and humans. Hoxa9, Meis1 and Pbx1 proteins have been shown to physically interact with each other, as Hoxa9 cooperatively binds consensus DNA sequences with Meis1 and with Pbx1, while Meis1 and Pbx1 form heterodimers in both the presence and absence of DNA. In this study, we sought to determine if Hoxa9 could transform hemopoietic cells in collaboration with either Pbx1 or Meis1. Primary bone marrow cells, retrovirally engineered to overexpress Hoxa9 and Meis1a simultaneously, induced growth factor-dependent oligoclonal acute myeloid leukemia in <3 months when transplanted into syngenic mice. In contrast, overexpression of Hoxa9, Meis1a or Pbx1b alone, or the combination of Hoxa9 and Pbx1b failed to transform these cells acutely within 6 months post-transplantation. Similar results were obtained when FDC-P1 cells, engineered to overexpress these genes, were transplanted to syngenic recipients. Thus, these studies demonstrate a selective collaboration between a member of the Hox family and one of its DNA-binding partners in transformation of hemopoietic cells.
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HoxA9 is overexpressed in 70% of AML cases, and overexpression of this transcription factor alone is sufficient to immortalize murine bone marrow derived myeloid cells.
“The transcription factor HoxA9 is overexpressed in 70% of AML cases, and overexpression of this transcription factor alone is sufficient to immortalize murine bone marrow derived myeloid cells (Ayton and Cleary, 2003; Golub et al., 1999; Kroon et al., 1998).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Kroon et al., 1998
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- Authors
- Kroon, E., Krosl, J., Thorsteinsdottir, U., Baban, S., Buchberg, A. M., & Sauvageau, G.
- Affiliations
- Montreal Clinical Research Institute (CA)
- Sidney Kimmel Cancer Center (US)
- Corresponding author
- Sauvageau, Guy
- Venue
- The EMBO Journal
- Published
- 1998-07-01
- Volume
- 17
- Issue
- 13
- Pages
- 3714-3725
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170707
- OpenAlex
- W2171482205
- Cited by
- 640
- References
- 56
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 18 · 2021: 22 · 2020: 23 · 2019: 18 · 2018: 13 · 2017: 32 · 2016: 28 · 2015: 33 · 2014: 30 · 2013: 39 · 2012: 36
- FWCI
- 8.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- 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
- HOXA9, homeodomain transcription factor, leukemic transformation, acute myeloid leukemia, bone marrow cells, hematopoietic cells, protein-protein interaction, heterodimerization, FDC-P1 cells, retroviral overexpression, syngeneic transplantation
- MeSH terms
- Pre-B-Cell Leukemia Transcription Factor 1, Myeloid Ecotropic Viral Integration Site 1 Protein, Animals, Bone Marrow Cells, Cell Line, Cell Transformation, Neoplastic, Cells, Cultured, DNA-Binding Proteins, Female, Genetic Vectors, Humans, Leukemia, Myeloid, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Neoplasm Proteins, Proto-Oncogene Proteins, Research Design, Retroviridae, Cell Transplantation, Homeodomain Proteins, Mice
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