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Chimaerism and erythroid marker expression after microinjection of human acute myeloid leukaemia cells into murine blastocysts

Oncogene volume 22, pages 9185–9191 (2003)Cite this article

Abstract

It has been suggested that the embryonic microenvironment can control the survival and the transformed phenotype of tumour cells. Here, we addressed the hypothesis that the murine embryonic microenvironment can induce the differentiation of human tumour cells. To examine such interactions, we injected human leukaemic cells into preimplantation murine blastocysts at embryonic day 3.5 of gestation (E3.5). Microinjection of human KG-1 myeloid leukaemia cells and primary human acute myeloid leukaemia (AML) cells led to the generation of chimaeric embryos and adults. We observed that in E12.5 murine embryos, KG-1 cells were preferentially detected in yolk sac and peripheral blood, while primary AML cells mainly seeded the aorta gonad mesonephros region of chimaeric embryos. Analysis of the donor contribution in 15 different adult tissues showed that progeny of primary AML cells seeded to various haematopoietic and nonhaematopoietic tissues. Chimaeric embryos and adults showed no apparent tumour formation. Furthermore, analysis of chimaeric E12.5 embryos revealed that the progeny of human KG-1 cells activated erythroid-specific human globin and glycophorin A expression. In summary, our data indicate that human AML cells activate markers of erythroid differentiation after injection into early murine embryos.

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Acknowledgements

Special thanks go to Rolf Kemler for drawing our attention to the regulatory effect of the embryonic microenvironment on tumour cells and to Ilse Junghahn for KG-1 and EOL cells. We thank Randall Cassada, Erin Drew and the members of the Müller lab for comments and critical reading of the manuscript. This work was supported in part by grants from the Würzburger Universitätsbund and the Wilhelm Sander-Stiftung to AMM.

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Author notes

  1. Friedrich Harder

    Present address: Develogen AG, 37079, Göttingen, Germany

  2. Michael Dürr and Friedrich Harder: Both authors contributed equally to the work

Authors and Affiliations

  1. Institute of Medical Radiation and Cell Research (MSZ), University of Würzburg, Versbacherstr 5, Würzburg, D-2 97078, Germany

    Michael Dürr, Friedrich Harder, Angela Merkel & Albrecht M Müller

  2. Department of Medicine III, University of Frankfurt, Frankfurt, 60590, Germany

    Gesine Bug

  3. Institute of Transfusion Medicine and Immune Haematology, Red Cross Blood Center, Frankfurt, 60528, Germany

    Reinhard Henschler

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  1. Michael Dürr
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Correspondence to Albrecht M Müller.

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Dürr, M., Harder, F., Merkel, A. et al. Chimaerism and erythroid marker expression after microinjection of human acute myeloid leukaemia cells into murine blastocysts. Oncogene 22, 9185–9191 (2003). https://doi.org/10.1038/sj.onc.1207134

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