title: [Treatment outcome of multidrug resistance related mRNA expression and c-jun-N-terminal kinase activity in patients with acute myeloid leukemia].
abstract: BACKGROUND
  The multidrug resistance (mdr1), multidrug resistance associated protein (mrp1), and glutathione-s-transferase (gst) pi genes have been associated with treatment failure in acute myeloid leukemia (AML). c-jun N-terminal kinase (JNK) activity is increased in response to chemotherapeutic agent.
  
  
  METHODS
  To investigate the significance of multidrug resistance (mdr) parameters and JNK activity, bone marrow or peripheral blood cells from 52 patients with AML were analyzed. RT-PCR was performed for mdr1, mrp1, and gst pi gene expression. JNK expression and activity were measured using an immunoe- nzymatic kinase assay and a western blot method.
  
  
  RESULTS
  High level expression of mdr1, mrp1, and gst pi mRNA was observed in 38.5%, 48.1% and 54.3% of AML cases, respectively. The remission rate was significantly low in cases with an older age (>55 yr), a high WBC count, poor chromosomal abnormalities, a high level expression of mdr1 and mrp1. The WBC count and mdr1 mRNA expression were independent predictors for the outcome to induction chemotherapy. There was a shorter duration of overall survival in the patients with an older age, a high WBC count, chromosome aberrations, high level expressions of mdr1 and mrp1 mRNA, and JNK activation. The patient's age, WBC count and chromosomal abnormalities were independent predictors for overall survivals. The majority (28/30) of AML cases did not show any levels of JNK activation except for two cases, which were associated with an extremely high WBC count, chromosomal aberration, high level expressions of mdr1, mrp1 and gst pi mRNA, and treatment resistance.
  
  
  CONCLUSIONS
  These data indicate the influences of mdr1 and mrp1 mRNA expression on the clinical outcome of AML to induction chemotherapy. But it will be necessary to investigate further whether blast cells of AML resistant to chemotherapy retain the capacity to activate JNK, and relate to MDR parameters.
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea.
authors: Jeong Hwa
authors: JH
authors: Do
authors: Seung Hwan
authors: SH
authors: Oh
authors: Eun Ju
authors: EJ
authors: Song
authors: Joo Seop
authors: JS
authors: Chung
authors: Chi Duk
authors: CD
authors: Kang
authors: Eun Yup
authors: EY
authors: Lee
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051549:Glutathione S-Transferase pi; D048031:JNK Mitogen-Activated Protein Kinases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger