title: Knockdown of PRAME enhances adriamycin-induced apoptosis in chronic myeloid leukemia cells.
abstract: OBJECTIVE
  Leukemia is resistant to currently available chemotherapy, and new strategies have been proposed to improve its efficacy. Such an approach requires know of the mechanisms involved in the resistance and survival of leukemia cells. Previous studied has found that Preferentially Expressed Antigen of Melanoma (PRAME) is overexpressed in the leukemia cells, and knockdown of PRAME promoted apoptosis in leukemia K562 cells. In the present study, we investigated whether inhibition of PRAME could sensitize K562 cells to chemotherapy.
  
  
  METHODS
  K562 cells were treated with PRAME siRNA, and/or adriamycin (ADR), and cell viability and apoptosis, mRNA and protein expression levels were, then, evaluated. Furthermore, the efficacy of PRAME siRNA combined with ADR was further examined in established xenograft models.
  
  
  RESULTS
  PRAME suppression was sufficient to induce spontaneous apoptosis of K562 cells. PRAME knockdown showed antiproliferative effects and induced tumor regression in established K562 xenograft models. ADR showed antitumor activity against K562 cells, co-treatment with PRAME siRNA induced an increased apoptosis rate than the sum of the single-treatment rates and promoted tumor regression without enhanced body weight loss in the K562 xenograft models.
  
  
  CONCLUSIONS
  PRAME is responsible for the inherent low levels of spontaneous apoptosis in K562 cells. The combination of PRAME siRNA with ADR induced more intense apoptosis compared with each single treatment. PRAME siRNA in combination with ADR is well tolerated and shows greater efficacy than either agent alone in mouse xenograft models.
authors.affiliation: Department of Medical Imaging, People's Hospital of Rizhao, Rizhao, China. lysrmyyblood@126.com.
authors.forename: H
authors.initials: H
authors.lastname: Yan
authors.forename: R-M
authors.initials: RM
authors.lastname: Zhao
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Wang
authors.forename: F-R
authors.initials: FR
authors.lastname: Zhao
authors.forename: S-L
authors.initials: SL
authors.lastname: Wang
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C404944:PRAME protein, human; D004317:Doxorubicin