EXPRESSION OF MULTIDRUG RESISTANCE GENE-1 IN LYMPHOMA

Summary and conclusionMultidrug resistance in cancer is a clinical problem, so it is a major cause of chemotherapeutic failure and patients death in haematooncology. MDR is related to expression of MDR-1 gene that encodes for 170 KD P- glycoprotein (P-gp) that function as transmemrane drug efflux Pump expell the drug out of the tumor cells.Over expression of P-gp and MDR-1 has been documented in lymphoma.Relapsed lymphoma highly express MDR-1 gene.Many methods used for detection of MDR-1 gene, in this study we use Rt-PCR for detection of MDR-1 gene.This study was carried out on 41 subjects. They were classified into 10 apparently healthy subjects as control group and 31 patients with lymphoma divided into 2 groups : 13 newly diagnosed lymphoma patients, 5 of them were HD and 8 were NHLs, while 18 lymphoma patients in relapse,4 of them were HD and 14 patients were NHLs .All members of the study were subjected to thorough clinical examination, routine investigations including CBC, liver and kidney function tests, measurement of serum LDH, BM exmination (patients only) and measurement of MDR-1 gene by real time PCR .This work was planned to measure the level of MDR – 1 gene expression in patients with lymphoma and analyze the correlation between its level and some laboratory parameters to determine its prognostic role in lymphoma. Also to detect the relation between MDR-1 and response to therapy after 3 months of treatment. In addition we compare the level and the rate of MDR-1 gene in newly diagnosed and relapsed patients to detect its role in chemotherapeutic failure.The results were statistically analysed and revealed the following:The mean values of age in lymphoma groups didn’t show any significant difference with control group ( group I ). Also, no statistical significant difference was abserved among the studied groups as regrad sex .A significant decrease in the mean values of haemoglobin level and platelets count among lymphoma patients when compared with the control group.The mean value of serum LDH level was found to be significantly higher in groups II and III when compared to the control group.Furthermore, the level of MDR-1 gene was found to be significantly higher in group II ( newly diagnosed patients ) and group III ( patients in relapse) as compared to group I (control group ) . Also there was a significant increase in the level of MDR-1 gene in group III when compared to group II.There were 23.1% (3/13) of our patients in group II had MDR-1 (+ve) while in group III (patients in relapse) 61.1%. (11/18) had MDR-1 (+ve). This result showed a significant increase in the prevelance of MDR-1 gene in group III when compared to group II.In group II of our patients the response rate to chemotherapy were 70% (7/10) in MDR-1 (–ve) cases while non of MDR-1 +ve cases responded to therapy. In group III, the response rate were 71.5% (5/7) in MDR-1 (-ve ) cases while 36.4% (4/11) of MDR-1 +ve cases responded to therapy.There was no significant difference in the mean value of MDR-1 level between both HD and NHL groups . Also our results revealed that prevelance of MDR-1 (+ve) cases didn’t show any significant difference between HD and NHL groups (44.4% and 45.5% respectively).The group of patients who were negative for MDR-1 expression had a significantly higher level of Hb and platelets count when compared to those group who were positive for MDR-1 expression.The level of LDH was significantly higher in patients group who were positive for MDR-1 expression than those who were negative.Furtheremore, we found a significant negative correlation between the level of MDR-1 gene expression and the Hb level . Also, there was significant positive correlation between MDR-1 expression and LDH level.Conclusion :From the previous results it was concluded that multidrug resistance due to expression of MDR-1 gene is an important factor in the course of patients with lymphoma. In addition MDR-1 gene may be used as a marker for prognosis and monitoring response to treatment in malignant lymphoma patients.