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.
This meta-analysis suggests there was no association between MDR1C3435T polymorphism and children ALL risk in overall populations, but significant association with an increased risk in Asians.
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).
The mdr1 gene or its glycoprotein product, P-glycoprotein, is detected with high frequency in secondary acute myeloid leukemia (AML) and poor-risk subsets of acute lymphoblastic leukemia.
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.
With respect to the negative controls, MCF7 and HL-60 cell lines, increased GST pi and mdr1 mRNA levels, expressed as arbitrary units (U), were respectively detected both in AML and in ALL patients.
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.
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.
The ABCB1 and ABCG2 gene expression levels were analyzed using real-time polymerase chain reaction in 61 patients diagnosed with ALL and 99 healthy donors as controls.
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 evaluated the effect of resveratrol and prednisolone on DNA methylation patterns of MDR1 gene promoter in the CCRF-CEM cell line as a representative for acute lymphoblastic leukemia.
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.
MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma.
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.
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 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.
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.
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.