Project description:Allogeneic hematopoietic stem cell transplantation remains the most efficacious treatment for many hematological malignancies. However, its therapeutic potential is affected by the most prominent side effect graft versus host disease. Despite advances in the treatment of graft versus host disease in recent years, morbidity and mortality remains high, which requires the development of new treatment approaches. In vitro, we have observed an upregulation of MHC / HLA molecules in several AML cell lines after treatment with the menin-inhibitor MI-463. We hypothesize that menin-inhibition increases the graft-versus-leukemia effect via targeting and sensitizing MLL-mutant AML cells, thus enhancing HLA-dependent killing.
Project description:Allogeneic hematopoietic stem cell transplantation remains the most efficacious treatment for many hematological malignancies. However, its therapeutic potential is affected by the most prominent side effect graft versus host disease. Despite advances in the treatment of graft versus host disease in recent years, morbidity and mortality remains high, which requires the development of new treatment approaches. In vitro, we have observed an upregulation of MHC / HLA molecules in several AML cell lines after treatment with the menin-inhibitor MI-463. We hypothesize that menin-inhibition increases the graft-versus-leukemia effect via targeting and sensitizing MLL-mutant AML cells, thus enhancing HLA-dependent killing.
