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Immunology

Allogeneic bone marrow transplantation and donor lymphocyte infusion in a mouse model of irradiation-induced myelodysplastic/myeloproliferation syndrome (MD/MPS): evidence for a graft-versus-MD/MPS effect

Leukemia volume 23, pages 340–349 (2009)Cite this article

Abstract

The role of graft-versus-malignancy reactivity in the effects of allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion (DLI) for myelodysplastic syndromes is as yet not well established. Clinical data are limited and animal models are scarce. Here, we report on the effects of allogeneic bone marrow transplantation (alloBMT) and DLI in a novel model of irradiation-induced murine myelodysplastic/myeloproliferation syndrome (MD/MPS). Total body irradiation with 8.5 Gy in SJL/J mice gave rise to a lethal wasting syndrome in 60% of mice, characterized by 1° normocellular bone marrow with dysplastic features in erythroid, myeloid and megakaryocytic cell lineages, 2° lymphosplenomegaly with spleens harboring a prominent extramedullary hematopoiesis with erythroid, myeloid and megakaryocytic lineages exhibiting dysplastic features, and foci of dysplastic hematomyelopoiesis in the liver, 3° peripheral thrombocytopenia and 4° evidence of disseminated infection or leukemic transformation in selected animals. This clinicopathological picture was consistent with a murine form of MD/MPS. Syngeneic or allogeneic (BALB/c) T cell-depleted BMT could not prevent the occurrence of lethal MD/MPS. In contrast, DLI at weeks 2–4 after BMT led to restoration of the dysbalanced hematomyelopoiesis. However, severe DLI-induced acute graft-versus-host disease occurred, precluding a survival advantage. We present evidence of the existence of a post-alloBMT DLI-induced graft-versus-MD/MPS effect in murine irradiation-induced MD/MPS.

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Acknowledgements

Gregor Verhoef and Michel Delforge are gratefully acknowledged for critical reading of the manuscript. This work was supported by grants from the Flanders Fund for Scientific Research, the Belgian Federation against Cancer and the WOMS (Scientific Research Multiple Sclerosis) Foundation. Bénédicte Dubois is supported by the University Research Council of the University of Leuven, Belgium. Ben Sprangers and Bart Van Wijmeersch are doctoral fellows, An D Billiau a postdoctoral fellow of the Flanders Fund for Scientific Research.

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Authors and Affiliations

  1. Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium

    B Sprangers, B Van Wijmeersch, A Luyckx, L De Somer, O Rutgeerts, C Lenaerts, M Waer & A D Billiau

  2. Laboratory of Neuroimmunology, University of Leuven, Leuven, Belgium

    B Van Wijmeersch & B Dubois

  3. Stem Cell Institute Leuven, University of Leuven, Leuven, Belgium

    A Luyckx

  4. Department of pathology, University of Leuven, Leuven, Belgium

    X Sagaert & C De Wolf-Peeters

  5. Laboratory of Experimental Oncology and Radiotherapy, University of Leuven, Leuven, Belgium

    W Landuyt

  6. Department of Laboratory Medicine, Laboratory of Hematology, University of Leuven, Leuven, Belgium

    N Boeckx

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  1. B Sprangers
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Correspondence to A D Billiau.

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Statement of authorship

BS, BVW and ADB designed and performed all experiments, some of which assisted by AL and LD, and analyzed all data. OR and CL provided technical assistance. WL performed irradiation. AL and NB performed analysis of CBC and BM smears. XS and CD-P performed pathological studies. BS and ADB wrote the manuscript. BD and MW oversaw the study and critically revised the manuscript.

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Sprangers, B., Van Wijmeersch, B., Luyckx, A. et al. Allogeneic bone marrow transplantation and donor lymphocyte infusion in a mouse model of irradiation-induced myelodysplastic/myeloproliferation syndrome (MD/MPS): evidence for a graft-versus-MD/MPS effect. Leukemia 23, 340–349 (2009). https://doi.org/10.1038/leu.2008.298

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