Effect on bone marrow mesenchymal stromal cells of mouse models of acute myeloid leukemia of different genotypes. Mus musculus

We found that cells of acute myeloid leukemia (AML) affect the transcriptome of mesenchymal stromal cells (MSC) in bone marrow (BM) involved by AML. Gene expression in BM-MSC of AML-bearing mice differed from that in BM-MSC of control mice; some gene changes were the same across different types of AML produced by well-known fusion oncogenes, while others were specific to certain genotypes. There were notable differences between the effects of tp53 WT and tp53-/- AML with the same oncogene (MLL&FLT3-ITD); these were supported by in vitro experiments in which normal BM-derived MSC were cultured with the same tp53 WT and tp53-/- pair of AML cells. Overall design: We established syngeneic AML, produced by different known AML fusion oncogenes, in C57BL/6 mice and isolated their BM-MSC. Gene expression profiling was used to compare AML-exposed MSC to those of control mice. BM-derived normal MSC were also cultured in vitro with tp53 WT and tp53-/- AML cells of the same genotype (MLL/ENL+FLT3-ITD).