Abstract
Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP), and lung resistance protein (LRP) may confer the phenotype of resistance to the treatment of neoplasias. To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR), and to determine the correlation between expression and event-free survival and clinical and laboratory variables. A retrospective clinical study. Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005). The presence of the common acute lymphoblastic leukemia antigen (CALLA) was correlated with increased LRP expression (p = 0.009) and increased risk of relapse or death (p = 0.05). The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05), as confirmed by multivariate analysis of the three genes studied (p = 0.035). Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the object of prospective studies.
Highlights
Despite the great advances in the cure rate for acute lymphoblastic leukemia (ALL), approximately 25% of affected children present disease recurrence.[1]
Thirty bone marrow samples from children with acute lymphoblastic leukemia were collected upon diagnosis and two upon relapse
Cell resistance to drugs is a determinant of the response to chemotherapy and radiotherapy and its detection may be of clinical relevance
Summary
Despite the great advances in the cure rate for acute lymphoblastic leukemia (ALL), approximately 25% of affected children present disease recurrence.[1]. The description of the multiple drug resistance protein (MDR-1), called pglycoprotein, seemed to be promising for the understanding of the mechanisms of antineoplastic treatment failure.[4] Subsequently, other drug resistance genes were described, among them genes related to resistance (multidrug resistance-related protein, MRP) and genes for the lung resistance protein (LRP). It appears that none of these can fully explain the pathways that effectively lead to the occurrence of tumor resistance
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