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Expression of DLK1 in hematopoietic cells results in inhibition of differentiation and proliferation

Oncogene volume 24, pages 4472–4476 (2005)Cite this article

Abstract

The Delta-like (DLK1) gene is overexpressed in CD34+ cells from myelodysplastic syndrome (MDS) patients. DLK1 encodes an EGF-like homeotic transmembrane protein homologous to the notch/delta/serrate family. Although exogenous DLK1 promotes maintenance of murine hematopoietic stem cells, the functional effects of DLK1 overexpression in hematopoietic cells are unknown. We show that ectopically expressed DLK1 significantly inhibits differentiation and proliferation of human promyelocytic HL-60 cells. Unlike preadipocytes, where proteolytic processing of membrane-bound protein and release of a soluble form mediates differentiation inhibition, proteolytic release of the extracellular domain was not required for inhibition of hematopoietic cell differentiation. However, intracellular domain interactions were critical to this DLK1 function. We conclude that DLK1 overexpression in hematopoietic cells has important functional consequences. Our studies identify novel molecular mechanisms and indicate that DLK1 has activity both as a soluble and a transmembrane expressed protein. Our results support further investigation of the role of DLK1 in abnormal hematopoiesis in MDS.

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Acknowledgements

We thank Tinisha McDonald and Helen Xu for their excellent technical assistance. This work was supported in part by the Leukemia Lymphoma Society of America Translational Research Award 6165-02. Ravi Bhatia is a Clinical Scholar of the Leukemia and Lymphoma Society.

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  1. Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, 91010, USA

    Liang Li, Stephen J Forman & Ravi Bhatia

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Li, L., Forman, S. & Bhatia, R. Expression of DLK1 in hematopoietic cells results in inhibition of differentiation and proliferation. Oncogene 24, 4472–4476 (2005). https://doi.org/10.1038/sj.onc.1208637

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