Gene Expression and Survival of Acute Lymphoblastic Leukemia Cells After Allogeneic Transplant

Background/Aim: This study explored the mechanisms of the allogeneic graft versus leukemia effect in acute lymphoblastic leukemia (ALL) cells by examining whether they change gene expression in the post-transplant environment containing cytokines and the immunosuppressant cyclosporine, and if such c...

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Bibliographic Details
Published in:Anticancer research 2021-06, Vol.41 (6), p.2781-2793
Main Authors: SCHENONE, DOMINIC, ANDOLINA, JEFFREY R., RADEMACHER, BROOKS, FOUNTAINE, THOMAS J., EDWARDS, ELENA, NUNEZ, LETI, QIU, MICHELLE, SHARMA, SONAKSHI, MULLEN, CRAIG A.
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Biological activity
Cell death
Cell proliferation
Cell survival
Cyclosporins
Cytokines
Flow cytometry
Gene expression
Gene flow
Gene set enrichment analysis
Genes
Leukemia
Leukocytes
Lymphatic leukemia
Lymphocytes
Lymphocytes T
Mesenchyme
Morphogenesis
Natural killer cells
Survival
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Summary:Background/Aim: This study explored the mechanisms of the allogeneic graft versus leukemia effect in acute lymphoblastic leukemia (ALL) cells by examining whether they change gene expression in the post-transplant environment containing cytokines and the immunosuppressant cyclosporine, and if such changes affect ALL cell survival. Materials and Methods: RNASeq was used to assess leukemia global gene expression and flow cytometry to measure ALL survival in the presence of T cells, NK cells, cytokines, and cyclosporine. Results: A total of 4,805 genes were differentially expressed. Gene set enrichment analysis demonstrated up-regulation of biological processes related to cytokine responses, control of viral infection, and regulation of leukocyte function including proliferation. Down-regulated genes were related to mesenchymal tissue morphogenesis. ALL cells exposed to cytokines and cyclosporine retained susceptibility to T and NK cell killing, and also exhibited increased cell death without exposure to killer cells. Conclusion: A significant portion of the graft versus leukemia effect may be mediated by cytokines and cyclosporine.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.15059