[Study of CYP3A5 in drug resistance mechanisms in acute leukemia].

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Wang T, Chen FY, Han JY, Shao NX, Ou-Yuang RR

[Study of CYP3A5 in drug resistance mechanisms in acute leukemia].

Zhonghua Xue Ye Xue Za Zhi. 2003 Jun;24(6):286-9.

PubMed ID

12859862 [ View in PubMed

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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). CONCLUSION: CYP3A5 expressed in leukemia cells may cause in situ metabolization of many kinds of anticancer drugs, thus led to drug resistance.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Daunorubicin	Cytochrome P450 3A5	Protein	Humans	Unknown	Inducer	Details