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Selected Works of Charalampos Papachristou
Article
Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells
Haematologica (2018)
  • Maria Krevvata, University of Pennsylvania
  • Xiaochuan Shan, University of Pennsylvania
  • Chenghui Zhou, University of Pennsylvania
  • Cedric Dos Santos, University of Pennsylvania
  • Georges Habineza Ndikuyeze, University of Pennsylvania
  • Anthony Secreto, University of Pennsylvania
  • Joshua Glover, University of Pennsylvania
  • Winifred Trotman, University of Pennsylvania
  • Gisela Brake-Silla, University of Pennsylvania
  • Selene Nunez-Cruz, University of Pennsylvania
  • Gerald Wertheim, Children's Hospital of Philadelphia
  • Hyun-Jeong Ra, University of Pennsylvania
  • Elizabeth Griffiths, Roswell Park Cancer Institute
  • Charalampos Papachristou, Rowan University
  • Gwenn Danet-Desnoyers, University of Pennsylvania
  • Martin Carroll, University of Pennsylvania
Link
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.
Keywords
  • Mesenchymal Stem Cells,
  • myelodysplastic syndromes,
  • acute myeloid leukemia
Disciplines
Publication Date
June 1, 2018
DOI
10.3324/haematol.2017.183202
Citation Information
Maria Krevvata, Xiaochuan Shan, Chenghui Zhou, Cedric Dos Santos, et al.. "Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells" Haematologica Vol. 103 Iss. 6 (2018) p. 959 - 971 ISSN: 1592-8721
Available at: http://works.bepress.com/charalampos-papachristou/6/