title: [Study of CYP3A5 in drug resistance mechanisms in acute leukemia].
abstract: OBJECTIVE
  To investigate if CYP3A5 is involved in drug resistances mechanisms of acute leukemia.
  
  
  METHODS
  By using RT-PCR, immunohistochemistry and MTT assay, CYP3A5 mRNA and protein were detected in leukemia cell lines and acute leukemia patients, meanwhile transcriptional regulation of CYP3A5 induced by daunorubicin was observed. A pcDNA3-CYP3A5 reconstituted plasmid and its stably transfected cell line HL-60/CYP3A5 were both established.
  
  
  RESULTS
  CYP3A5 mRNA was detected in K562 and U937 cells, whose IC(50) values of daunorubicin were 2.1-fold higher than those of NB4 and HL-60 cells. Bone marrow CYP3A5 positive blast cell percentage at the time of diagnosis in primary drug resistance group (17.2%) was significantly higher than that of continuous complete remission (CCR) group (0.4%) and secondary drug resistance group (5.4%). In their first complete remission of the early relapsed group, the positive rate had been 23.9% as compared with that of CCR group (1.3%). Daunorubicin increased CYP3A5 mRNA level in K562/A02 and activated its transcription in HL-60/ADR. HL-60/CYP3A5 cell was significantly resistant to daunorubicin and vincristine than HL-60 cells did (3.0 and 4.0 times, respectively).
  
  
  CONCLUSIONS
  CYP3A5 expressed in leukemia cells may cause in situ metabolization of many kinds of anticancer drugs, thus led to drug resistance.
authors.affiliation: Hematology Department, Renji Hospital of Shanghai Second Medical University, Shanghai Institute of Hematology, Shanghai 200001, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Fang-yuan
authors.initials: FY
authors.lastname: Chen
authors.forename: Jie-ying
authors.initials: JY
authors.lastname: Han
authors.forename: Nian-xian
authors.initials: NX
authors.lastname: Shao
authors.forename: Ren-rong
authors.initials: RR
authors.lastname: Ou-Yuang
mesh_terms: D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology*; D003630:Daunorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D003630:Daunorubicin