The Clinical Research Of Breast Cancer Resistance Protein Gene In Acute Myelocytic Leukemia

The leukemia is one of the most familiar malignant diseases in mankind, the death rate occupies to the 6-8th in the malignant tumor,and stand first in child and crowds under 35 years of ages.In our country,the adult leukemia regards the acute leukemia as principle,accounting for 80%in total of leukemia,and the acute myelocytic leukemia(AML)be known as the majority (1.62/100,000).The chemistry medicine treatment is still the first choose with AML now,it's complete release(CR)rate can reach to 60%-80%,but most sufferers relapse within 2 years,the second chemotherapy curative effect isn't good,the further research confirmed someone who is in initial treatment but not easily to release and most recidivists bear a multidrug resistance(MDR),as a result,the research of the drug resistant mechanism in leukemia and the choice of sensitive medicine treatment are the keys,which would raise chemotherapy curative effect and prolong the patient duration even to cure.The BCRP is a recently detection and a new medicine of ejecting medicine as a pump which related the tumor multidrug resistance,be a kind of the half transport.In the last few years,the researchs of BCRP in domestic and international were indicated that the BCRP bears drug resistance and prognosis of AML,being an independent factor of the AML drug resistance,and there wasn't any correlation with the classic MDR.The research discovers that the increase of BCRP mRNA expression hints the possibility of the disease relapse.BCRP mRNA level is so important to the judge of prog and the treatment in patients.For inquiry into the relationship of BCRP and the clinical characteristic,the medicine sensitivity,the prog of AML,this research chooses 20 AML hospitalization from three affiliated hospitals of jilin university and so on.Median age is 41.5 years old(21-55),male 8 examples(40%),feminine 12 examples(60%)among them.By the FAB typing,M₁ 1 example,M₂ 4 examples,M₃ 6 examples,M₄ 3 examples,M₅ 6 example.Matched contro1:5 examples,AA 1 example,nomal 2 examples and ITP 2 examples among them.According to the course of illness,there is divided into the initial treatment set and the replase set.According to the clinic diagnosis standard,is divided into the sensitiveness set and the drug resistance set.we adopt RT-PCR to examine 5 matched controls and the expression level of the BCRP gene in the pit cell of 20 AMLs;FCM examines the BCRP protein level in marrow pit cells of 20 AML samples;Combine the usage MTT method that observed the medicine sensitivity at a different density (2.5-40ug/ml)of a anti- tumor medicine.The results showing:The BCRP mRNA of 20 AML sufferers expresses quantity in high and low dissimilarity,the expressed level in control and AMLs shows an individual difference,from 0-1.950.The average expression level of 5 normal persons is 0.047±0.040,the expression level of 20 AML sufferers is 0.302±0.331,was analysised by covariance having the difference (P=0.002).In 20 AMLs,7 BCRP mRNA expressions are masccline,13 express negative.In 12 examples of the initial treatment AML sufferers,5 examples express masculine of the BCRP mRNA,CR1 1 example,CR1 rate is 20.0%;The BCRP mRNA expressing negative are 7 examples,CR1 5 examples,the CR1 rate is 71.4%,the difference have already shown the covariance meaning(P=0.0000).Combine the related data of the clinic diagnosis,the BCRP mRNA of the initial sensitive treatment set is lowest,average is 0.052±0.037;The relapse set and drug resistance set are higher,0.254±0.288 and 0.372±0.364.Leaming by covariance examination,there had covariance meaning among the initial sensitive treatment set and the replase set,drug resistance set(P＜0.05).But it's no meaning between the replase set and drug resistance set(P＞0.05).the BCRP masculine in 5 initial sensitive set is 1 example,the masculine rate is 20%,the BCRP masculine in 11 drug resistance set are 5 examples,the masculine rate reaches to 45.4%,learning by statistical analyzation have the difference(P＜0.05).In 20 AMLs,in addition to M₁,M₆,the M₇ number less,in 5 second types,all have the expression of BCRP gene.M₅ 6 examples,the BCRP opposite expression level is the tallest,measure to 0.340±0.368,M₂ 4 examples,the expression level is lowest,measure to 0.177±0.269,but the analysis learning by covariance didn't show the difference(P=0.206).In each type,the masculine rate of the BCRP gene expression also has difference.The M₅ is the tallest,there be 3 masccline examples in 6 samples,the rate is 50%,then M₃,M₄,M₂ secondly,distinguish to 33.3%,33.3%,25%,through the analysis,its difference didn't show meaning.The BCRP protein expression have different degree in relapse set,initial sensitive treatment set and drug resistance set,the difference shows meaning (P＜0.05),but relapse set and drug resistance set,the difference doesn't show meaning(P＞0.05).9 examples are masculine of BCRP protein expression in 20 AML sufferers,at different clinical stage,the masccline rate dissimilarity,the initial sensitive treatment set is lowest,an only 5 examples are masculine,the rate is 20%(1/5),3 masculine in 8 relapse examples,the rate is 37.5%(3/8),the masculine rate of the clinic drug resistance set is tallest,45.4%.(5/11).And in mRNA related analytical manifestation,4 examples express negative of the BCRP protein but the mRNA expression is masculine,both have no relativity.The inhibition ratio of DNR checks single cell with 20 AMLs is difference,16-folds densities is higher than single density,equally inhibition ratio is(33.87±16.36)%,(16.3±18.37)%,there is presented a density dependence phenomenon.Regard to the high sensitive examples in 20 AMLs,there are 4 examples under the 16-folds densities,under the single density it si only for 1 example,the difference has already shown statistic meaning(P＜0.05).At single density,the inhibition ratio of DNR to the initial sensitive treatment set is(27.59±25.12)%,the drug resistance set is(11.03±14.55)%,the difference didn't have meaning(P=0.115).Under the 16-folds density,the inhibition ratio of DNR to the initial sensitive treatment set shows(44.49±20.89)%,the drug resistance set is(20.89±9.34)%,the difference shows meaning(P=0.025).Under the single density,the inhibition ratio of DNR to the negative set is(24.09±18.68)%,the masccline set is(1.99±0.80)%,there has a statistic meaning(P=0.001).Under 16-folds densities,the inhibition ratio of DNR to the negative expression set is(39.26±15.25)%,the masccline expression set is(20.58±3.67)%(P=0.002).On the whole,the CR rate of the BCRP mRNA masccline be lower than negative in the initial treatment AML;compareing the BCRP gene expression level of the clinical drug resistance set and the sensitive set,the former is obviously high in the latter;The BCRP expression of each AML type didn't show difference obviously;The expression level of the BCRP protein comparison,the initial treatment sensitive set and drug resistance set,relapses set show much difference,but relapses set and drug resistance set doesn't show difference;The repellency to medicine of the different BCRP expression cell a obvious amount of-effect relation(P＜0.05).Under 16-fold densities,comparing the inhibition ratio of NDR cure,the sensitive set is super than the drug set, BCRP mRNA masccline set be super than negative set(P＜0.05).