| Multidrug resistance ( MDR) will eventually result in failure of chemotherapy in patients with acute leukemia. It involves in several reasons , the over expression of multidrug resistance associated protein ( MRP) play a more important role in it, and MRP includes multidrug resistance associated protein 1 ( MRP1) and lung resistance associated protein (LRP).MRP1 is a transmembrane - protein, which can transport intracellular drugs outside at the existence of GSH and ATP, lower the accumulation of several an-tileukemia drugs ( eg. ADR, VP - 16 and VCR) . LRP is a component of the major vault protein complex located in the cytoplasm and at the nuclear pore, mediate the bidirectional transport of substance between the nucleus and cytoplasm, lower intracellular drug accumulation via promoting drug efflux, such as anthra-cyclines, epipodophyllotoxins, platins,etc. Expression of MRP1 and LRP study in 52 patients with acute leukemia and 12 normal donors by using immunohisto-chemistry method to reveal the correlation between multidrug resistance and prognosis in leukemia.Methods1. Patients:Acute leukemia(AL)52 cases, male 23,female 29, median age was 37. 1 13. 8 years, all patients were confirmed according to FAB diagnostic standard. Acute myeloid leukemia( AML) 42/52, M1, 5, M2 8, M3 6, M4 5, M5 13, M61, MDS - AML 4; Acute lymphoblastic leukemia 10/52, L1 2, L2 8 . 12 normal donors's bone marrow as control, male 8 , female 4, median age was 35. 8 13.2 years.2. Isolation of mononuclear cells;3 -5ml heparinized peripheral blood or bone marrow sample were obtained, mononuclear cells were isolated with Ficoll density gradient centrifugation.3. Detection of MRPl and LKP expression:MRPl and LRP expression were measured by immunohistochemistry and if positive cell 15% difinated positive.4. Statistical analysis:spss 6.2 ,x2analysis, pearson analysis was used to analyze the correlation between expression of MRPl and LRP.Results1. Expression of MRPl and LRP in AL and donors:Expression of MRPl was detected in 15 of 52 (28. 8% ) patients with acute leukemia,expression of LRP was detected in 22 of 52(42. 3% ) patients with a-cute leukemia, there was no expression of MRPl in normal donors, whereas the expression of LRP was only 1 in 12 donors. Co - expression of MRPl and LRP was detected in 9 of 52(17. 3% ) ,24 of 52 (46. 2% ) without any expression .2. Correlation between expression of MRPl, LRP and the prognosis : Complete remission rate in patients with MRPl expression was detected in 5of 15 (33. 3% ), whereas in patients without MRPl expression was 22 of 37 (59.5% ), the difference show no significance( p >0.05).Complete remission rate 31. 8% (7/22) was lower in patients with LRP expression than in those(73.3% , 22/30) without LRP expression, the difference was significant( p <0. 05). Complete remission rate (22. 2% , 2/9 )in patients with MRPl and LRP co - expression was lower than in those (75% , 18/24) without any expression ,the difference was significant ( p <0.01).3. Relationship between MRPl and LRP : MRPl and LRP were detected concurrently in 52 patients with acute leukemia, LRP was positive in 9 of 15 patients with acute leukemia expressing MRPl, and 12 express LRP in 37 patients with acute leukemia without MRPl expression.DiscussionMRP1 gene was located on the short arm of chromosome 16, at 16pl3.1, encoded a 190kd transmembrane - protein, which belong to the superfamily of ATP binding cassette (ABC) transporter proteins. The main mechanism of which seems to function as an drug efflux pump or decreasing the accumulation of drug via altering drug diffusion and then result in drug resistance. Lohri's report show that the expression of MRP1 have a relationship with FAB subtype, especially lower in FAB M4 and M5 than others. Leith reported that expression of MRP1 demonstrating a marginally significant decreasing trend with increasing age, the same result also showed in our study. The corealation between MRP1 and prognosis in acute leukemia is still conflicting, so...
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