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Primitive erythropoiesis in infantile haemangioma

Authors

  • T. Itinteang,

    1. School of Biological Sciences, Victoria University of Wellington, Box 600, Wellington, New Zealand
    2. Centre for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
    3. Gillies McIndoe Research Institute
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  • S.T. Tan,

    1. School of Biological Sciences, Victoria University of Wellington, Box 600, Wellington, New Zealand
    2. Centre for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
    3. Gillies McIndoe Research Institute
    4. University of Otago, Dunedin, New Zealand
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  • H.D. Brasch,

    1. Centre for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
    2. Gillies McIndoe Research Institute
    3. Department of Pathology, Hutt Hospital, Wellington, New Zealand
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  • A. Vishvanath,

    1. School of Biological Sciences, Victoria University of Wellington, Box 600, Wellington, New Zealand
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  • D.J. Day

    1. School of Biological Sciences, Victoria University of Wellington, Box 600, Wellington, New Zealand
    2. Centre for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
    3. Gillies McIndoe Research Institute
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  • Funding sources
    This work is supported by grants from the Wellington Regional Plastic Surgery Unit Research & Education Trust, the Wellington Medical Research Foundation, the Surgical Research Trust, Pub Charities and the Cancer Society of New Zealand. A.V. was supported, in part, by the Cancer Society of New Zealand. T.I. is supported by the Royal Australasian College of Surgeons’ Foundation for Surgery Scholarship.

  • Conflicts of interest
    None declared.

  • S.T.T. and D.J.D. contributed to this study as equal senior authors.

Darren J. Day.
E-mail: Darren.Day@vuw.ac.nz

Summary

Background  Infantile haemangioma (IH) is a tumour of the microvasculature composed predominantly of proliferating endothelial cells. It expresses markers associated with endothelial, haematopoietic and mesenchymal lineages. We have previously shown that the cells forming the capillary endothelium of proliferating IH express cell surface markers and transcriptions factors consistent with it being a haemogenic endothelium.

Objectives  We wished to determine whether the expression of transcription factors associated with the erythroid lineage was of physiological relevance and sufficient for IH tissue cultured in vitro to undergo erythropoiesis.

Methods  Immunohistochemical staining of paraffin-embedded sections of proliferating IHs was undertaken and expression of the embryonically associated haemoglobin ζ (HBZ) chain and the erythropoietin receptor (EPO-R) was determined. Relative expression of mRNA encoding these proteins was determined by quantitative reverse transcription–polymerase chain reaction using snap-frozen biopsy samples. Differentiation towards erythrocytes was investigated using freshly resected tissue cultured as explants in Matrigel.

Results  The endothelium of the microvessels, but not the pericyte layer, was strongly immunoreactive for the EPO-R and the embryonically associated HBZ chain. Abundant expression of transcripts encoding these proteins was also detected, corroborating the immunohistochemical staining. When tissue was grown in culture the cells emanating from IH explants were able to generate enucleated erythrocytes in vitro. The erythrocytes were immunoreactive for the erythrocyte-specific marker glycophorin A.

Conclusions  The microvessels in IH are a functional haemogenic endothelium that expresses the embryonically associated HBZ chain and is able to form erythrocytes in vitro. IH thus represents a possible extramedullary site for tumour-associated primitive erythropoiesis.

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