Gene expression changes induced by BAY1436032 (IDH1mut inhibitor) in sorted human (CD45+) cells from bone marrow of IDH1mut patient derived xenotransplantation mice model

Mutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis. NSG mice were transplanted with cells from a human AML patient carrying IDH1mutation. After 60-70% chimerism, mice were treated either with vehicle or with 150mg/kg/day dose of BAY1436032 perorally. Four weeks after treatment, human CD45+ cells were sorted from mouse bone marrow, from which total RNA was extracted and subjected to microarray analysis.