Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia Journal Article

Authors: Jacamo, R.; Davis, R. E.; Ling, X.; Sonnylal, S.; Wang, Z.; Ma, W.; Zhang, M.; Ruvolo, P.; Ruvolo, V.; Wang, R. Y.; McQueen, T.; Lowe, S.; Zuber, J.; Kornblau, S. M.; Konopleva, M.; Andreeff, M.
Article Title: Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia
Abstract: 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 (BMMSC) 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. © Jacamo et al.
Keywords: genotype; stroma; microenvironment; aml; gep
Journal Title: Oncotarget
Volume: 8
Issue: 48
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2017-10-13
Start Page: 83354
End Page: 83369
Language: English
DOI: 10.18632/oncotarget.19042
PROVIDER: scopus
PMCID: PMC5663521
PUBMED: 29137349
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Scott W Lowe
    144 Lowe
  2. Weirui Ma
    4 Ma