Clinical Significance Of P-gp And BCRP Gene Expression In Acute Myeloblastic Leukemia

Objective:To investigate the relationship between the expression of P-glycoprotein(P-gp) and the breast cancer resistance protein (BCRP) gene in acute myeloblastic leukemia (AML).Method:(1)Using semi-quantitative reverse transcription polymerase chain reaction(RT-PCR)assay andβ-actin as positive reference ,we detected the expression of BCRP gene in 41 AML samples and 20 patients with non-maligance hematology disease as a control group.(2)The expression rate of P-gp in bone marrow mononuclear cells(BMMNC) from 41 AML sample and 20 nornal controls was detected by flow cytometry with direct immunofluorescent labeling.Result:(1) The result showed that there were no significant difference between the positive percentage of P-gp in AML and that of normal control group .(22.0% vs10.0%,P>0.05)； The positive percentage of BCRP gene expression in AML was higher than that of normal control group(61.0% vs 15.0%,P<0.05). (2) The positive percentage of P-gp was expressed higher at relapsed/refractory group as compared to diagnosis group(42.9% vs17.6%,P<0.05),but there were no significant difference in the positive percentage of BCRP gene expressed patients at relapsed/refractory group as compared to diagnosis group(71.4% vs 58.8%, P>0.05). (3)NO significant association was found between P-gp and FAB subtype(P>0.05);BCRP gene expression correlated with FAB subtype(P<0.05),the higher and lower expression of BCRP gene were observed in M3 subtype and M4 subtype, respectively.(4)The complete remission (CR)rate in patients with P-gp+ and BCRP + were lower than that in patients with P-gp- and BCRP–(42.9% vs81.5%,40.0vs 92.9% ,P<0.05);The early relapse rates of patients with P-gp + and BCRP + were higher than that in patients with P-gp- and BCRP -(100% vs36.4%, 62.5% vs15.4% ,P<0.05) 。(5) Compared with patients with P-gp-/BCRP-,The patients with P-gp+/BCRP+ were characteristic of lower CR rate and early relapse rates(0% vs 81.8% ,P<0.01; 100% vs 22.2%, P<0.05).(6)No significant correlation between P-gp and BCRP was found by linear regression analysis at relapsed/refractory group as compared to diagnosis group (ｒ=0.01, r=0.08 ,p>0.05). (7)BCRP gene expression in Acute promyelocytic leukemia was high, but it couldn,t assess the prognosis.Conclusion:(1)Clinical resistance to chemotherapy in AML is closely associated with expression of P-gp and BCRP . (2)High expression of P-gp and BCRP are adverse prognosis factors in de novo AML. Evaluation of P-gp and BCRP co-expression play an important role in AML. (3)The correlation between P-gp and BCRP was not found .(4) BCRP gene expression in Acute promyelocytic leukemia were high, but it couldn,t assess the prognosis.