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Oncogenes, Fusion Genes and Tumor Suppressor Genes

The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation

Leukemia volume 24, pages 1910–1919 (2010)Cite this article

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Abstract

The t(6;9)-positive acute myeloid leukemia (AML) is classified as a separate clinical entity because of its early onset and poor prognosis. The hallmark of t(6;9) AML is the expression of the DEK/CAN fusion protein. The leukemogenic potential of DEK/CAN has been called into question, because it was shown to be unable to block the differentiation of hematopoietic progenitors. We found that DEK/CAN initiated leukemia from a small subpopulation within the hematopoietic stem cell (HSC) population expressing a surface marker pattern of long-term (LT) HSC. The propagation of established DEK/CAN-positive leukemia was not restricted to the LT-HSC population, but occurred even from more mature and heterogeneous cell populations. This finding indicates that in DEK/CAN-induced leukemia, there is a difference between ‘leukemia-initiating cells’ (L-ICs) and ‘leukemia-maintaining cells’ (L-MCs). In contrast to the L-IC cells represented by a very rare subpopulation of LT-HSC, the L-MC seem to be represented by a larger and phenotypically heterogeneous cell population.

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Acknowledgements

This work was funded by a grant from Deutsche Krebshilfe e.V. to Martin Ruthardt (107741). MR is further funded by grants from German José Carreras Leukemia-Foundation (together with RH—DJCLS—R 07/27f), Deutsche Forschungsgemeinschaft (DFG-RU 728/3-2) and Alfred and Angelika Gutermuth Foundation.

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Authors and Affiliations

  1. Department of Hematology, Goethe University, Frankfurt, Germany

    C Oancea & M Ruthardt

  2. Department of Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany

    B Rüster & R Henschler

  3. Institute of Molecular Biology and Tumor Research, Phillipps-University, Marburg, Germany

    E Puccetti

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  1. C Oancea
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  2. B Rüster
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  4. E Puccetti
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Correspondence to M Ruthardt.

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Oancea, C., Rüster, B., Henschler, R. et al. The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation. Leukemia 24, 1910–1919 (2010). https://doi.org/10.1038/leu.2010.180

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