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).
Therefore, the objective of this study was to assess the effect of metformin on the treatment regimen in patients with ALL who exhibited high levels of ABCB1 gene expression and to determine its impact on overall survival.
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.
High expression of MDR1 and BCL-2 in AML and MRP1 gene in ALL was associated with response to induction chemotherapy (p=0.001, p=0.02 and p=0.007 respectively).
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.
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).
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.
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.
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.