- Volume 16 Issue 15
DOI QR Code
High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia
- Bhatia, Prateek (Department of Paediatrics, Advanced Pediatric Centre) ;
- Masih, Shet (MDRL Laboratories) ;
- Varma, Neelam (Department of Hematology, Post Graduate Institute of Medical Education and Research (PGIMER)) ;
- Bansal, Deepak (Pediatric Hemato-oncology Unit, Department of Paediatrics, Post Graduate Institute of Medical Education and Research (PGIMER)) ;
- Trehan, Amita (Pediatric Hemato-oncology Unit, Department of Paediatrics, Post Graduate Institute of Medical Education and Research (PGIMER))
- Published : 2015.10.06
Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy 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 standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations 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 noted in 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 LRP positive 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 cases were 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 early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.
ALL;chemotherapy;drug resistance proteins;pediatric;response
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