Resistance of T-cell acute lymphoblastic leukemia to tumor necrosis factor−related apoptosis-inducing ligand-mediated apoptosis

Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors

“…17,19,37 Cell surface expression of DR4 and DR5 was clearly detectable on all four t(17;19)-ALL cell lines except for HAL-O1, which showed marginal expression of DR4, whereas that of DcR1 and DcR2 was almost undetectable (Figure 2a). Strong correlations were observed between the sensitivity of a cell line to rhsTRAIL and its cell surface expression of DR4 (r ¼ 0.666, Po0.0001) and DR5 (r ¼ 0.539, P ¼ 0.0012) (Figure 2b and Supplemental Figure 2).…”

“…Strong correlations were observed between the sensitivity of a cell line to rhsTRAIL and its cell surface expression of DR4 (r ¼ 0.666, Po0.0001) and DR5 (r ¼ 0.539, P ¼ 0.0012) (Figure 2b and Supplemental Figure 2). When compared with various B-precursor ALL cell lines (Figure 2c), the RFI of DR4 on t(17;19)-ALL cell lines (median 1.9) was significantly higher than that on MLL þ (median 1.0, P ¼ 0.0055), Ph1-positive (median 1.05, P ¼ 0.0330) 17 and other B-precursor ALL cell lines (median 1.0, P ¼ 0.0127) 37 by Mann-Whitney analysis. In addition, the RFI of DR5 was higher than 1.4 in all 4 t(17;19)-ALL cell lines, whereas it was p1.3 in 5 of 9 MLL þ , 2 of 6 Ph1-positive, and 8 of 13 other B-precursor ALL cell lines.…”

“…Viability of the primary samples was determined by staining with trypan blue. 37 The D viability (%) of samples from the patients with Ph1-positive ALL, MLL þ ALL, T-ALL or T-non-Hodgkin lymphoma, calculated as: (% viability in the absence of rhsTRAIL) À (% viability in the presence of rhsTRAIL), was determined when percent viability of background was 460%. 37 …”

“…For quantitative real-time PCR of DR4 and DR5 transcripts, triplicated samples containing 9 ml of cDNA with 10 ml of Taqman Universal PCR Master Mix (Applied Biosystems, Foster City, CA, USA) and 1 ml of 20Â Assays-on-demand Gene Expression Product (DR4; Hs 00269492_m1, DR5; Hs 00366272_m1, Applied Biosystems) were preincubated at 50 1C for 2 min and subsequently at 95 1C for 10 min. 37 Amplification was performed by 40 cycles of reaction at 95 1C for 15 s and 60 1C for 1 min. Fluorescence data were quantitatively analyzed on an ABI Prism 7500 Sequence Detection System (Applied Biosystems).…”

Multi-level disruption of the extrinsic apoptotic pathway mediates resistance of leukemia cells to TNF-related apoptosis-inducing ligand (TRAIL)

“…4). TRAIL-resistance of leukemia cells [6,35,37,38]. In this study we analyzed molecular mechanisms responsible for TRAILresistance of K562 cell line and the nature of TRAIL-sensitivity of two TRAIL-sensitive K562 clones (S1, S2) established by limiting-dilution approach from the original K562 cell line.…”