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MN1-TEL, the product of the t(12;22) in human myeloid leukemia, immortalizes murine myeloid cells and causes myeloid malignancy in mice

Leukemia volume 20, pages 1582–1592 (2006)Cite this article

Abstract

MN1-TEL is the product of the recurrent t(12;22)(p12;q11) associated with human myeloid malignancies. MN1-TEL functions as an activated transcription factor, exhibiting weak transforming activity in NIH3T3 fibroblasts that depends on the presence of a functional TEL DNA-binding domain, the N-terminal transactivating sequences of MN1 and C-terminal sequences of MN1. We determined the transforming activity of MN1-TEL in mouse bone marrow (BM) by using retroviral transfer. MN1-TEL-transduced BM showed increased self-renewal capacity of primitive progenitors in vitro, and prolonged in vitro culture of MN1-TEL-expressing BM produced immortalized myeloid, interleukin (IL)-3/stem cell factor-dependent cell lines with a primitive morphology. Transplantation of such cell lines into lethally irradiated mice rescued them from irradiation-induced death and resulted in the contribution of MN1-TEL-expressing cells to all hematopoietic lineages, underscoring the primitive nature of these cells and their capacity to differentiate in vivo. Three months after transplantation, all mice succumbed to promonocytic leukemia. Transplantation of freshly MN1-TEL-transduced BM into lethally irradiated mice also caused acute myeloid leukemia within 3 months of transplantation. We infer that MN1-TEL is a hematopoietic oncogene that stimulates the growth of hematopoietic cells, but depends on secondary mutations to cause leukemia in mice.

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Acknowledgements

We thank Blake McGourty for the supply of C57BL/6/129svJ-mixed background mice and technical assistance. We gratefully acknowledge Ann-Marie Hamilton Easton and Richard Ashmun for expert FACS analysis, and we thank Charlette Hill for editing the manuscript. We are grateful to Luc van Rompaey who initiated these experiments. This work was supported by NCI Grant CA72999, the cancer center (CORE) support grant CA217G and by the American Lebanese Syrian Associated Charities (ALSAC).

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  1. C Carella and J Bonten: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN, USA

    C Carella, J Bonten & G C Grosveld

  2. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    J Rehg

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  1. C Carella
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Correspondence to G C Grosveld.

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Carella, C., Bonten, J., Rehg, J. et al. MN1-TEL, the product of the t(12;22) in human myeloid leukemia, immortalizes murine myeloid cells and causes myeloid malignancy in mice. Leukemia 20, 1582–1592 (2006). https://doi.org/10.1038/sj.leu.2404298

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