scholarly journals Early responses to tumor necrosis factor of human promyelocytic leukemia cell lines sensitive and resistant to the factor.

1988 ◽  
Vol 13 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Kazuhide Takahashi ◽  
Shunsuke Yanoma ◽  
Tetsuo Ono
2015 ◽  
Vol 44 (3) ◽  
pp. 327-329 ◽  
Author(s):  
Tatsuya Sakaguchi ◽  
Kenta Mine ◽  
Fuki Kudoh ◽  
Rui Kamada ◽  
Kazuyasu Sakaguchi

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2477-2477 ◽  
Author(s):  
Hayato Tamai ◽  
Koichi Miyake ◽  
Hiroki Yamaguchi ◽  
Masahiro Okabe ◽  
Kazuo Dan ◽  
...  

Abstract Abstract 2477 Mixed-lineage leukemia (MLL)/AF4 positive acute lymphoblastic leukemia (ALL), which is common in infant leukemia, is associated with a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The resistance to graft versus leukemia (GVL) effect may be the possible reason of the poor effect of allo-HSCT on MLL/AF4 positive ALL. Cytotoxic effector mechanisms, which are mediated by tumor necrosis factor-alpha (TNF-alpha), Fas ligand (FasL), or perforin were reported to contribute to GVL effect. We analyzed the sensitivity to TNF-alpha of MLL/AF4 positive ALL cell lines (SEM and RS4;11) together with MLL/AF4 negative leukemia cell lines (MOLT4, Raji and K562) and found that the growth inhibition by TNF-alpha of MLL/AF4 positive ALL cell lines group was significantly lower than those of another MLL/AF4 negative leukemia cell lines group (P<0.01). To examine the possible mechanism of resistance to TNF-alpha of MLL/AF4 positive leukemia, we focused on S100A6 as a possible factor, since it was reported that expression of S100A6, which is a calcium-binding protein implicated in many cellular processes and often up-regulated in cancers limits apoptosis induced by TNF-alpha through p53 inactivation in cardiac myocytes. Western Blot analysis showed that significant up-regulation of S100A6 expression and inhibition of acetyl p53/p53 expression were observed only in MLL/AF4 positive ALL cell lines in the presence of TNF-alpha (5ng/ml)(P<0.01 for S100A6 and P<0.01 for acetyl-P53/p53). To confirm the effect of S100A6 on the resistance to TNF-alpha of MLL/AF4 positive ALL cell lines, we examined the apoptosis rate of MLL/AF4 positive ALL cell lines treated with small interfering RNA (siRNA) against S100A6. TUNEL assay showed that significantly increased rate of apoptosis under s100A6 siRNA in the presence of TNF-alpha (control siRNA VS s100A6 siRNA; 42.5%&mnplus;4.5% VS 90.0%&mnplus;5.0%, P<0.01 for SEM, 32.5%&mnplus;3.5% VS 87.5%&mnplus;5.0%, P<0.01 for RS4;11). Western Blotting also showed that these apoptosis were mediated by p53-Caspase8 pathway. Up-reguration of S100A6 and inhibition of p53-Caspase8 pathway were also confirmed in previously established MLL/AF4 transgenic mice. These results suggest that MLL/AF4 positive ALL escapes from TNF-alpha mediated apoptosis by up-regulation of S100A6 expression followed by interfering with p53 acetylation. Our present results suggest that S100A6 may be a promising therapeutic target for MLL/AF4 positive ALL by combinating with allo-HSCT. Disclosures: No relevant conflicts of interest to declare.


1995 ◽  
Vol 19 (10) ◽  
pp. 681-691 ◽  
Author(s):  
H.G. Drexler ◽  
H. Quentmeier ◽  
R.A.F. MacLeod ◽  
C.C. Uphoff ◽  
Z.-B. Hu

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