The Mechanism of Trans-activation of theMDR1Gene by Human T-Cell Leukemia Virus

Decitabine (5-Aza-2′-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells

“…For example, NF-IL6 binding site was shown to be more important than GCboxes in MDR-1 regulation in HTLV-1 infected cell lines. 25 Furthermore, Fryxell et al 26 described the methylation status of the CpG-rich domain as not acting as a switch regulating MDR-1 gene expression. Intracellular levels of various transcriptional factors may vary in cells, which may explain these conflicting results.…”

Efficacy and mechanism of action of the proteasome inhibitor PS-341 in T-cell lymphomas and HTLV-I associated adult T-cell leukemia/lymphoma

“…Conventional chemotherapy has limited benefit in ATL patients given that HTLV-1 cells carry an intrinsic resistance to chemotherapy due to frequent overexpression of the multidrug resistance protein (Lau et al, 1998) and the lung resistance protein (Ikeda et al, 1999). In addition, the constitutive activation of NF-kB, the inhibition of p53 function and the downregulation of Fas-ligand expression in HTLV-I-positive cells (Tamiya et al, 1998) likely protect these cells from chemotherapy-induced apoptosis.…”

Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes

“…Briefly, like ALL and CLL, acute and chronic ATL appear to be biologically and clinically quite different, although both ATL sub-types are caused by HTLV-I infection. Details of molecular mechanisms of co-activation of MRP and LRP genes by HTLV-I require further investigation in chronic ATL, analogous to the study on HTLV-I tax protein and NF-IL6 in the MDR1 promoter (Lau et al, 1998a).…”