High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia


Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistanceto drugs. Materials and
Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrugresistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong.
Results:The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standardrisk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrenttranslocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%)and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was notedin 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15(53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRPpositive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%)LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive caseswere in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05).
Conclusions:Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to earlytreatment and hence can be used as a prognostic marker. However, larger prospective studies with longer followup are needed, to understand the clinical relevance of drug resistance proteins.