ATP-binding cassette subfamily B member 1 (ABCB1) is a recognized factor which causes MDR and is closely related to poor outcome and relapse in leukemia.
We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer.
The cytotoxic studies have demonstrated a higher sensitivity of the leukemia lines to DOX-BNNPs compared with the carcinoma lines: IC<sub>50</sub>(DOX-BNNPs) is 1.13, 4.68, 0.025, and 0.14 μg/mL for the KB-3-1, MDR KB-8-5, K562, and MDR i-S9 cell lines, respectively.
Expression dynamics of drug resistance genes, multidrug resistance 1 (MDR1) and lung resistance protein (LRP) during the evolution of overt leukemia in myelodysplastic syndromes.
These findings indicate that siRNA specifically and efficiently interferes with the expression of mdr1 and could be used as a molecularly defined therapeutic approach for MDR in the treatment of leukemia.
In an attempt to identify the target protein, P-GP or mrp, of each MDR antagonist, verapamyl (Ver), dipyridamole (Dip), or cyclosporin A (Cy-A), this study was designed to compare the activity of the three afore-mentioned drugs and to test their combined effect on the cidal activity of vincristine (VCR) in five types of wild and the corresponding VCR-resistant cultured cell lines from human leukemia and lymphoma.
Here, two GO-resistant variants (HL/GO-CSA [225-fold], HL/GO [200-fold]) were established by serially incubating human leukemia HL-60 cells with GO with or without a P-glycoprotein (P-gp) inhibitor, cyclosporine A, respectively.
Since therapeutic strategies are being developed to circumvent drug resistance by inhibiting P-gp, prospective studies concerning the clinical relevance of P-gp in childhood leukemia are warranted.
It is known that the drug efflux protein, P-glycoprotein (P-gp), and inhibitors of apoptosis proteins (IAPs) are involved in the MDR of leukemic cells, but their roles in leukemia infiltration have not been clearly elucidated.
To understand the mechanism that underlies the emergence of cells with such gene alterations in human leukemia, we performed clonal analysis of the gene expression of mutant dihydrofolate reductase (DHFR) and mdr1 in trimetrexate-resistant human leukemia MOLT-3 cells.
Although innumerable reports have been published in which P-gp has been shown to confer MDR to malignant (including leukemia) cells, so far, large-scale studies in the clinical setting have not convincingly proven that MDR1 plays a major role in clinical drug resistance when the influence of other known prognostic factors in human leukemia are taken into account.
For this purpose, human leukemia K562 cells with varying expression levels of ABCB1 were used: drug selected K562/Dox and K562/HHT cells with very high transporter expression, and K562/DoxDR2, K562/DoxDR1, and K562/DoxDR05 cells with gradually decreased expression of ABCB1 derived from K562/Dox cells using RNA interference technology.
In conclusion, these results suggested that the MDR1 TT genotype might influence risk of development of acute lympoblastic leukemia and the CC genotype might be linked to a poor prognosis of ALL.
Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients.
In the present study, long noncoding RNA (lncRNA) UCA1 was identified as an important modulator of MDR1 by a model system of leukemia cell lines with a gradual increase of MDR1 expression and IM resistance.
Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1-gene translocation in homoharringtonine-selected K562 human leukemia cell lines.