关键词: t(17, 19)-急性淋巴细胞白血病, 肿瘤坏死因子相关凋亡诱导配体, 移植物抗白血病, 细胞凋亡

Abstract:

Objective To observe the sensitivity of t(17;19) acute lymphoblastic leukemia (ALL) cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -mediated apoptosis and to discuss its possible mechanism and clinical significance.Methods 4 t(17;19)-ALL cell lines and a primary cell sample were used as experimental group and 28 other B-precursor ALL cell lines were used as control group.The cell surface expression of TRAIL receptors was detected by flow cytometry,and the inhibition of cell growth was measured by 3H-thymidine uptake assay after treated with rhsTRAIL.Early apoptosis was detected by flow cytometry using Annexin-V staining and the changes of apoptosis signaling pathway after incubation with rhsTRAIL were checked by immunoblotting assay. Results The cell surface expression of death receptor 4(DR4) in t(17;19)- ALL cells was significantly higher than that in other cell lines (P<0.05).The relative fluorescence intensity (RFI) of DR5 was higher than 1.4 while it was lower than 1.3 in other cell lines.The cell growth of t(17;19)-ALL was nearly 100% inhibited by rhsTRAIL at 100 μg/L,which was much higher than other cell lines (P<0.05 or P<0.01).The inhibition was blocked by RIK-2 (neutralizing antibody of TRAIL) and  z-VAD-fmk ( inhibitor of caspase).rhsTRAIL induced early apoptosis in t(17;19)-ALL cells and the apoptotic rate was much higher than that in negative control (P<0.05).Cleaved bands of caspase-8,Bid,caspase-3 and PARP were observed within2 h of incubation with rhsTRAIL. Conclusion t(17;19)-ALL cells are highly sensitive to TRAIL and eventually to graft versus leukemia (GVL).Allo-SCT should be performed in early stage to obtain long-term surviving in the patients with t(17;19)-ALL.

Key words: t(17;19) acute lymphoblastic leuk
emia;tumor necrosis factor-related apoptosis-inducing ligand, graft versus le
ukemia, apoptosis