TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000672860
  • Gene Name:VEGF
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:VEGF signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00877 (APRD00178, DB02439)
  • Drug Name:Sirolimus(Rapamycin)
  • Drug Method:down-regulated the gene expression the gene expression

Disease basic infommation

  • Disease:chronic myeloid leukemia
  • Tissue:cell lines and patients tissues

Other information

  • Title:Evaluation of antileukaemic effects of rapamycin in patients with imatinib-resistant chronic myeloid leukaemia
  • Journal:Eur J Clin Invest
  • Published:2008
  • PubMed ID:18173550
  • Abstract:Background:Recent data suggest that the mammalian target of rapamycin (mTOR) is involved in the regulation of growth of neoplastic cells in chronic myeloid leukaemia (CML). Patients and methods:We treated six patients with imatinib-resistant CML in haematological relapse (leukocytes > 20,000 microL(-1)) with rapamycin at 2 mg per os daily for 14 consecutive days, with dose-adjustment allowed to reach a target rapamycin serum concentration of 10-20 pg mL(-1). Results:A major leukocyte response with decrease to less than 10,000 microL(-1) was obtained in two patients, and a minor transient response was seen in two other patients. In responding patients, we also observed a decrease in vascular endothelial growth factor (VEGF) mRNA levels in circulating leukaemic cells. Side effects during rapamycin treatment were mild in most patients. In one patient, pneumonia developed. Rapamycin was also found to counteract growth of CML cells in vitro as determined by (3)H-thymidine incorporation. Moreover, rapamycin inhibited the growth of Ba/F3 cells exhibiting various imatinib-resistant mutants of BCR/ABL, including the T315I variant that exhibits resistance against most currently available BCR/ABL kinase inhibitors. Conclusions:Rapamycin shows antileukaemic effects in imatinib-resistant CML in vitro and in vivo. Larger trials with rapamycin or rapamycin-derivatives in combination with other targeted drugs are warranted to further determine clinical efficacy in CML.
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