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.
E2A-HLF-mediated over-expression of ABCB1 may play a critical role in defining the clinical phenotype of ALLs with a t(17;19), suggesting pharmacologic modulation of ABCB1 activity as a rational therapeutic strategy for this chemotherapy resistant subtype of ALL.
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.
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.
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.
Activation of the MDR1 upstream promoter (USP) has been described previously in four lymphoblastic leukemia patients, where it is the major MDR1 promoter associated with P-glycoprotein overexpression.
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.
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.
MDM2 induces NF-kappaB/p65 expression transcriptionally through Sp1-binding sites: a novel, p53-independent role of MDM2 in doxorubicin resistance in acute lymphoblastic leukemia.
Moreover, both AML and acute lymphoblastic leukemia patients with high MDR1 mRNA expression at diagnosis tended to show a low remission rate and short remission periods.
In conclusion, P-gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease-free survival.
In order to identify genomic changes associated with drug-resistance acquisition, we performed R-banding karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization to compare a human T-cell lymphoblastic leukemia cell line, CEM-wild type, and a subline with resistance to vinblastine (CEM-VLB) and overexpressing P-glycoprotein.
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.
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 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.
To clarify the function of the mdr3 P-gp, we examined the intracellular rhodamine123 (Rh123) levels of mdr1 P-gp-negative and mdr3 P-gp-positive leukemic cells from patients with acute lymphocytic leukaemia, on the addition of 10 microM cyclosporin A (CyA).
A similar strong association has been observed between the expression of P-glycoprotein and outcome of treatment in certain malignancies in children, such as neuroblastoma, rhabdomyosarcoma, and acute lymphoblastic leukemia.
We studied the mdr1 gene expression in 36 freshly established cell lines from 28 children with acute lymphoblastic leukemia (16 T-ALL, six BCP-ALL, two B-ALL (L3), two biphenotypic leukemias, two Burkitt's lymphomas).
To evaluate the frequency and the prognostic value of different mechanisms of drug resistance in acute leukemias, we investigated the expression of mdr1 by immunocytochemistry, mRNA slot blot or RT-PCR in 182 cases of adult acute myeloid and 37 cases of adult lymphoblastic leukemia.