Quantitative analysis of a MDRI transcript for prediction of drug resistance in acute leukemia

Shin Ichi Fujimaki, Tadao Funato, Hideo Harigae, Junko Fujiwara, Junichi Kameoka, Kuniaki Meguro, Mitsuo Kaku, Takeshi Sasaki

研究成果: Article査読

30 被引用数 (Scopus)

抄録

Background: Assessing the drug resistance of leukemic cells is important for treatment of leukemia. We developed a quantitative reverse transcription (RT)-PCR method for multidrug resistance 1 (MDR1) and multidrug resistance-related protein 1 (MRP1) transcripts to evaluate drug resistance, and applied it to clinical samples. Methods: The cutoffs for copy numbers of MDR1 and MRP1 transcripts were defined based on copy numbers in healthy bone marrow mononuclear cells. To confirm that the cutoffs reflected biological resistance, we established vincristine (VCR)-resistant K562 sublines that showed various degrees of drug resistance and examined the correlation between the copy numbers of these transcripts and the biological resistance of these clones. In addition, we compared the sensitivity and specificity of quantitative RT-PCR to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric (FCM) analysis. Results: The defined cutoff for copy numbers of MDR1 transcripts corresponded with the degree of biological resistance of VCR-resistant K562 sublines. Clinical study revealed that the concentrations of MDR1 mRNA in all relapsed patients with acute myelogenous leukemia (AML) were above the cutoff. Moreover, both AML and acute lymphoblastic leukemia patients with high MDR1 mRNA expression at diagnosis tended to show a low remission rate and short remission periods. No association was observed between the amounts of MRP1 transcripts and clinical outcomes. The specificity and sensitivity of quantitative RT-PCR for MDR1 were superior to the MTT assay and FCM analysis. Conclusion: These results suggest the efficacy of this quantitative analysis of MDR1 transcripts for the prediction of clinical drug resistance in acute leukemia.

本文言語English
ページ(範囲)811-817
ページ数7
ジャーナルClinical Chemistry
48
6
DOI
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • 臨床生化学
  • 生化学、医学

フィンガープリント

「Quantitative analysis of a MDRI transcript for prediction of drug resistance in acute leukemia」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル