Journal
ONCOTARGET
Volume 8, Issue 48, Pages 83354-83369Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19042
Keywords
AML; microenvironment; GEP; stroma; genotype
Categories
Funding
- National Institutes of Health/National Cancer Institute [P01 CA55164, CCSG P30 CA016672, SPORE P50 CA100632, SPORE P50 CA136411]
- Paul and Mary Haas Chair in Genetics
- Leukemia and Lymphoma Society grant [CDP-01]
- National Institutes of Health through M. D. Anderson's Cancer Center Support Grant [CA016672]
- [R01 CA155056]
- [DRP 5 P50 CA100632-08]
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The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or null genetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested. In addition, there were sets of differentially-expressed genes in AML-exposed BM-MSC that were unique to the particular AML genotype or Trp53 status. Our findings support the hypothesis that leukemia cells alter the transcriptome of surrounding BM stromal cells, in both common and genotype-specific ways. These changes are likely to be advantageous to AML cells, affecting disease progression and response to chemotherapy, and suggest opportunities for stroma-targeting therapy, including those based on AML genotype.
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