| The chemotherapy is the major and basic method to treat leukemia, and also the basis of the stem cell transplantation. During recent years, although many new chemotherapeutic drugs and protocols have been developed to treat leukemia, most patients ultimately died of treatment failure. There are many possibilities of the failure and drug resistance may be the most important factor. Many mechanisms can result in cellular multidrug resistance (MDR) including P-glycoprotein (P-gp), multidrug resistance associated protein (MRP),lung resistance protein(LRP) and breast cancer resistance protein(BCRP) which served as drug "pump" or "entrapment", altered apoptosis mechanisms, as well as enzymatic drug detoxification and so on. The following experiments were performed to investigate comprehensively the expression of drug resistance proteins and apoptosis modulating protein, and their relationship with the biological characters and prognosis in patients with acute- leukemia. That may provide the guide to tailor chemotherapy for individual patients and increase chemotherapeutic effect.HL-60/VCR cells were used as a good model to study acquired chemoresistance. The previous data showed that the mechanism of MDR was the overexpression of P-gp.In this study, flow cytometry was used to analyze the expression of MDR proteins including P-gp, MRP, LRP, BCRP and GST- n , apoptosis modulating proteins including bcl-2, bcl-X, bax and bad in HL-60/VCR and HL-60. The results showed that the expression of P-gp, MRP, BCRP, GST- n were 18.62, 1.19, 1.5, 1.32 -foldin HL-60/VCR as much as that in HL-60,respectiveIy, but LRP was not different between the two cell lines. The apoptosis modulating proteins of bcl-2, bcl-X, bad were 2.48, 1.25, 1.08 -fold in HL-60/VCR as much as in HL-60, respectively, while the pro-apoptosis protein bax decreased to 0.88-fold as mush as in HL-60. This study demonstrated that various MDR mechanisms were involved in HL-60/VCR,which including P-gp, MRP, BCRP and GST- n , the apoptosis modulating proteins bcl-2, bcl-X, bax and bad, and suggested that acquired chemoresistance were caused by several drug resistance mechanisms.The immunohistochemistry and RT-PCR have been used to measure the expression of bcl-2,bax in acute leukemia. In this study,flow cytometry was used to investigate the expression of bcl-2, bcl-X, bax, bad in 64 patients with de novo acute leukemia. We found that the expression of bcl-2 in acute myeloid leukemia(AML) was lower than that in acute lymphoid leukemia(ALL) (P<0.05). In AML subtypes, the expression of bcl-2 in Ml, M4 and M5 was significantly higher than that in M2, M3 (P<0.05), respectively. The expression of bax was higher in M4 than that in other AML subtypes (PO.05). The expression of bcl-X was higher in Ml, M2 M5 than that in M3, M4 (PO.05), respectively. The expression of bcl-2, bcl-X, bax and bad was not significantly different between chemoresistant and complete remission(CR) patients, respectively, but the ratio of bcl-2/bax was significantly higher in chemoresistant patients than that in patients achieving CR (PO.05). The CR rate was 48% in the high-risk group, which was significantly lower than 78.2% in the low-risk group (PO.05). It suggests that the ratio of bcl-2/bax may influence the therapeutic sensibility, and it is an independent prognostic factor in de novo AML. The CR rate was 33.3% in patients with high ratio of bcl-2/bax and high expression of bcl-X, which was lower than that in the patients with high ratio of bcl-2/bax and low expression of bcl-X (56.2%).Our study suggests that bcl-X might reinforce the ability of anti-apoptosis and increase the drug resistance.We further explored the correlation of the high ratio of bcl-2/bax with clinical and biological characteristics in de novo AML. We found that the high ratio of bcl-2/bax was more frequent in M4(80%),and then in M5(61.5%),M1(50%) and M2(38.8%),the lowest in M3(14.3%). The high ratio of bcl-2/bax was significantly associated with CD34 expression (P<0.05), and had no correlation with CD2, CD...
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