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Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis

Oncogene volume 24, pages 336–343 (2005)Cite this article

Abstract

In vitro studies have implicated the Lyn tyrosine kinase in erythropoietin signaling. In this study, we show that J2E erythroid cells lacking Lyn have impaired signaling and reduced levels of transcription factors STAT5a, EKLF and GATA-1. Since mice lacking STAT5, EKLF or GATA-1 have red cell abnormalities, this study also examined the erythroid compartment of Lyn−/− mice. Significantly, STAT5, EKLF and GATA-1 levels were appreciably lower in Lyn−/− erythroblasts, and the phenotype of Lyn−/− animals was remarkably similar to GATA-1low animals. Although young adult Lyn-deficient mice had normal hematocrits, older mice developed anemia. Grossly enlarged erythroblasts and florid erythrophagocytosis were detected in the bone marrow of mice lacking Lyn. Markedly elevated erythroid progenitors and precursor levels were observed in the spleens, but not bone marrow, of Lyn−/− animals indicating that extramedullary erythropoiesis was occurring. These data indicate that Lyn−/− mice display extramedullary stress erythropoiesis to compensate for intrinsic and extrinsic erythroid defects.

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Acknowledgements

We thank Dr Margaret Hibbs for making the Lyn−/− mice available and Shane Meakins for excellent technical assistance. This work was supported by grants from National Health and Medical Research Council (Grant 139008, 303101), the Cancer Foundation of Western Australia and the Medical Research Foundation of Royal Perth Hospital.

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Authors and Affiliations

  1. Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, WA, Australia

    Evan Ingley, David J McCarthy, Jessica R Pore, Mohinda K Sarna, Aini S Adenan, Michael J Wright, Peta A Tilbrook & S Peter Klinken

  2. PathCentre, The Queen Elizabeth II Medical Centre, Nedlands, WA, Australia

    Wendy Erber

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Ingley, E., McCarthy, D., Pore, J. et al. Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis. Oncogene 24, 336–343 (2005). https://doi.org/10.1038/sj.onc.1208199

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