Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells

Maria Krevvata, Xiaochuan Shan, Chenghui Zhou, Cedric dos Santos, Georges Habineza Ndikuyeze, Anthony Secreto, Joshua Glover, Winifred Trotman, Gisela Brake-Silla, Selene Nunez-Cruz, Gerald Wertheim, Hyun Jeong Ra, Elizabeth Griffiths, Charalampos Papachristou, Gwenn Danet-Desnoyers, Martin Carroll

    Research output: Contribution to journalArticlepeer-review

    12 Scopus citations

    Abstract

    Patient-derived xenotransplantation models of human myeloid diseases including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms are essential for studying the biology of the diseases in pre-clinical studies. However, few studies have used these models for comparative purposes. Previous work has shown that acute myeloid leukemia blasts respond to human hematopoietic cytokines whereas myelodysplastic syndrome cells do not. We compared the engraftment of acute myeloid leukemia cells and myelodysplastic syndrome cells in NSG mice to that in NSG-S mice, which have transgene expression of human cytokines. We observed that only 50% of all primary acute myeloid leukemia samples (n=77) transplanted in NSG mice provided useful levels of engraftment (>0.5% human blasts in bone marrow). In contrast, 82% of primary acute myeloid leukemia samples engrafted in NSG-S mice with higher leukemic burden and shortened survival. Additionally, all of 5 injected samples from patients with myelodysplastic syndrome showed persistent engraftment on week 6; however, engraftment was mostly low (<2%), did not increase over time, and was only transiently affected by the use of NSG-S mice. Co-injection of mesenchymal stem cells did not enhance human myelodysplastic syndrome cell engraftment. Overall, we conclude that engraftment of acute myeloid leukemia samples is more robust compared to that of myelodysplastic syndrome samples and unlike those, acute myeloid leukemia cells respond positively to human cytokines, whereas myelodysplastic syndrome cells demonstrate a general unresponsiveness to them.

    Original languageEnglish (US)
    Pages (from-to)959-971
    Number of pages13
    JournalHaematologica
    Volume103
    Issue number6
    DOIs
    StatePublished - Jun 3 2018

    All Science Journal Classification (ASJC) codes

    • Hematology

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