|
KMID : 0981820070270040229
|
|
Korean Journal of Laboratory Medicine
2007 Volume.27 No. 4 p.229 ~ p.236
|
|
|
Treatment Outcome of Multidrug Resistance Related mRNA Expression and c-Jun-N-Terminal Kinase Activity in Patients with Acute Myeloid Leukemia
|
|
Do Jeong-Hwa
Oh Seung-Hwan
Lee Eun-Yup
Song Eun-Joo
Chung Joo-Seop
Kang Chi-Duk
|
|
|
Abstract
|
|
|
Background:The multidrug resistance (mdr1), multidrug resistance associated protein (mrp1), and glutathione-s-transferase (gst) 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 gene expression. JNK expression and activity were measured using an immunoe- nzymatic kinase assay and a western blot method.
ResultsHigh level expression of mdr1, mrp1, and gst 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 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. (Korean J Lab Med 2007;27:229-36)
|
|
|
KEYWORD
|
|
|
Drug Resistance, JNK, AML
|
|
|
FullTexts / Linksout information
|
|
 
|
|
|
Listed journal information
|
|
  
|
|