From these observations it appears that overexpression without gene amplification of mdr-1/P-170 may be one mechanism of clinical drug resistance in ALL.
We found a concomitant increase in mdr1 and mrp gene expression combined with a decreased expression of topoisomerase II alpha in the course of the second relapse of an acute lymphoblastic leukemia (ALL).
In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTpi, and GSTmu.
We found a high frequency of MDR1 gene expression: 10 out of 20 with de novo acute myeloid leukemia (AML), 8 out of 17 with de novo acute lymphoblastic leukemia (ALL), and none of the 3 with de novo acute mixed leukemia, were MDR1 mRNA-positive.
We studied the expression of P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein (MRP), and major vault protein/lung resistance protein (LRP) in 141 children with acute lymphoblastic leukemia (ALL) and 27 with acute myeloid leukemia (AML) by flow cytometry.
In whole ALL, CD13/CD33 was associated closely with the presence of stem-cell antigen CD34, and in T-lineage ALL, CD13/CD33 had a significant correlation with additional stem-cell features, such as HLA-DR, multidrug resistance 1 (MDR1) and c-kit gene expression.
This in vitro study suggests that bcr-abl-positive ALL is relatively resistant to daunorubicin, but this resistance is not mediated through mdr1 gene expression.
Overexpression of the multidrug resistance gene, MDR1, is of prognostic relevance in acute myeloid leukemia, while its role in acute lymphoblastic leukemia (ALL) is still under debate.
Multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) gene expression in childhood acute lymphoblastic leukemia.
To explore this phenomenon we investigated N6/ADR, a doxorubicin-selected, P-gp-positive variant of the human acute lymphoblastic leukemia (ALL) cell line NALM6.
The expression of P-glycoprotein, multidrug-resistance protein, and lung-resistance protein (LRP) was not higher in infants compared to older c/preB ALL patients, but LRP was higher in proB ALL and MLL-rearranged ALL of all ages.
In conclusion, the results of the present study provide evidence that C3435TMDR1 polymorphism may involve both the susceptibility to and the clinical outcome of childhood ALL.
In a matched case-control study, we investigated the associations between CNS relapse in childhood ALL and the presence of phenotypically relevant single nucleotide polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding for Pgp; exon 26, C3435T).
From this study, it is clear that P-gp/170 is expressed to a higher degree in leukemic cells and this is greater in relapsed compared to de novo cases and more in AML than ALL blasts.
Buccal cell DNA from ALL cases (n = 294) and controls (n = 369) individually matched on gender, date of birth, Hispanic status, and maternal race were whole genome amplified and genotyped for four MDR1 SNPs, T-129C (rs3213619), C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642).
Expression of multidrug resistance 1 (MDR1), multidrug resistance-related protein 1 (MRP1), lung resistance protein (LRP), and breast cancer resistance protein (BCRP) genes and clinical outcome in childhood acute lymphoblastic leukemia.
The present study suggests that the genetic background of MDR1 may be associated with the development of childhood ALL, possibly due to a quantitative change in the MDR1 gene resulting from genetic polymorphisms.
To determine the influence of the MDR1C3435T polymorphism on the development of childhood acute lymphoblastic leukemia (ALL), we studied 107 children with ALL and 111 healthy subjects.
There were no relations between the presence of P-gp, clinical characteristics (age, sex, hepatomegaly, and splenomegaly) and initial laboratory parameters (immunophenotype, white blood cells count, and serum lactate dehydrogenase) in ALL.
In this study, we have shown that changes in the expression of MDR1 gene after short-term incubation of lymphoblasts with prednisolone may have prognostic value in pediatric de novo ALL patients.