Journal article
Enforced expression of HOX11 is associated with an immature phenotype in J2E erythroid cells
British Journal of Haematology, Vol.118(3), pp.909-917
2002
Abstract
The HOX11 gene encodes a homeodomain transcription factor that is essential for spleen development during embryogenesis. HOX11 is also leukaemogenic, both through its clinical association with childhood T-cell acute lymphoblastic leukaemia, and its ability to immortalize other haematopoietic cell lineages experimentally. To examine the pathological role of HOX11 in tumorigenesis, we constitutively expressed HOX11 cDNA in J2E murine erythroleukaemic cells, which are capable of terminal differentiation. Enforced HOX11 expression was found to induce a profound alteration in J2E cellular morphology and differentiation status. Our analyses revealed that HOX11 produced clones with a preponderance of less differentiated cells that were highly adherent to plastic. Morphologically, the cells overexpressing HOX11 were larger and had decreased globin levels, as well as a reduction in haemoglobin synthesis in response to erythropoietin (EPO). Immunocytochemical analysis confirmed the immature erythroid phenotype imposed by HOX11, with clones transfected with HOX11 demonstrating expression of the c-Kit stem cell marker, while retaining EPO receptor expression. Taken together, these results show that HOX11 alters erythroid differentiation, favouring a less mature progenitor-like stage. This supports the notion that disrupted haematopoietic cell differentiation is responsible for pre-leukaemic immortalization by the HOX11 oncoprotein.
Details
- Title
- Enforced expression of HOX11 is associated with an immature phenotype in J2E erythroid cells
- Authors/Creators
- W.K. Greene (Author/Creator)J. Ford (Author/Creator)D. Dixon (Author/Creator)P.A. Tilbrook (Author/Creator)P.M. Watt (Author/Creator)S.P. Klinken (Author/Creator)U.R. Kees (Author/Creator)
- Publication Details
- British Journal of Haematology, Vol.118(3), pp.909-917
- Publisher
- Blackwell Publishing Inc.
- Identifiers
- 991005540718807891
- Murdoch Affiliation
- School of Veterinary and Biomedical Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.108 Molecular & Cell Biology - Cancer & Development
- 1.108.207 Neural Crest
- Web Of Science research areas
- Hematology
- ESI research areas
- Clinical Medicine