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

Abstract

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.

Analysis of Peripheral Blood Mononuclear Cells Gene Expression Highlights the Role of Extracellular Vesicles in the Immune Response following Hematopoietic Stem Cell Transplantation in Children

“…Currently, gene expression in the context of the HSCT procedure is described primarily in the aspect of tracking the differentiation of transplanted hematopoietic stem cells [ 19 , 20 ] or in assessing the expression of genes related to the possibility of disease relapse and disease-free survival [ 21 , 22 , 23 , 24 ]. Moreover, it is known that the HSCT procedure with subsequent immunosuppressive treatment affects the expression of leukemic cells [ 25 ]. Our first attempt to assess this dependency in 2016 [ 26 ] resulted in a better understanding of the genetic background of immune complications after the HSCT procedure, but due to the improvement of available research tools and the updating of genetic databases, we decided to reassess the collected material.…”