title: [Role of c-Myc in mesenchymal stromal cell-mediated drug resistance in acute leukemia cells].
abstract: OBJECTIVE
  To explore the role of c-Myc in mesenchymal stromal cell-mediated drug resistance and elucidate the molecular mechanism of acute myeloid leukemia (AML) from the version of tumor microenvironment.
  
  
  METHODS
  AML cell lines U937 and KG1a were co-cultured with mesenchymal stromal cells (MSC) from bone marrow of healthy donors between January to March 2012. The AML cell lines plated alone was cultured as controls. Apoptosis induced by mitoxantrone was measured by flow cytometry and Annexin V/PI double and 4'-6-diamidino-2-phenylindole (DAPI) staining. And c-Myc protein was detected by Western blot under both culturing conditions. After a pre-treatment of c-Myc inhibitor 10058-F4, the apoptosis of AML cell was also evaluated.
  
  
  RESULTS
  Apoptosis of AML cells (U937 and KG1a) significantly decreased during co-culturing with MSC (9.88% ± 1.53% vs 42.83% ± 2.03%, P = 0.004;20.60% ± 2.87% vs 42.53% ± 5.29%, P = 0.030). Drug resistance was implicated. The co-culturing of AML cells with MSC significantly induced an up-regulation of c-Myc. The inhibition of c-Myc with 10058-F4 could induce apoptosis of AML cells. After an addition of 10058-F4 into the co-culture system, the apoptotic rate of KG1a cells significantly increased from 23.87% ± 1.55% to 57.23% ± 3.88% (P = 0.009). Similarly the apoptotic rates spiked from 16.07% ± 2.11% to 53.47% ± 4.08% in U937 cells (P = 0.004) to overcome the stromal cell-mediated drug resistance.
  
  
  CONCLUSIONS
  The co-culturing of AML cells and MSC induces an up-regulation of c-Myc protein so as to cause the emergence of chemoresistance. Therefore targeting c-Myc protein may provide a novel therapeutic strategy of AML.
authors.affiliation: Department of Hematology, Cancer Institute & Hospital, Tianjin Medical University, Tianjin Key Laboratory of Cancer Prevention & Therapy, Tianjin 300060, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.forename: Wei-peng
authors.initials: WP
authors.lastname: Zhao
authors.forename: Shan-qi
authors.initials: SQ
authors.lastname: Guo
authors.forename: Chen
authors.initials: C
authors.lastname: Tian
authors.forename: Yi-zhuo
authors.initials: YZ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D017209:Apoptosis; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016271:Proto-Oncogene Proteins c-myc