Differential CD95 expression and function in T and B lineage acute lymphoblastic leukemia cells

Abstract

recently, several bcl-2-related genes were cloned

In vitro susceptibility to TRAIL-induced apoptosis of acute leukemia cells in the context of TRAIL receptor gene expression and constitutive NF-κB activity

“…Despite the rather low number of TRAIL sensitive leukemic cell samples in this subtype, we found that precursor B cell ALL disclosed a higher in vitro susceptibility to TRAIL-induced apoptosis compared with AML and precursor T cell ALL. This is in contrast to the constitutive susceptibility to CD95(Fas/Apo-1)-induced apoptosis of leukemic cells: precursor B cell ALL cells were significantly less CD95-sensitive compared with precursor T cell ALL and AML cells 34,35,39 Compared with our previous studies on CD95-induced apoptosis in AML and precursor T cell ALL, these subtypes seem to be less sensitive to TRAIL-than to CD95-induced apoptosis. In contrast, precursor B cell ALL samples were rather more susceptible to TRAIL-than to CD95-induced apoptosis.…”

“…In contrast, precursor B cell ALL samples were rather more susceptible to TRAIL-than to CD95-induced apoptosis. 34,35,39 The independence of CD95 and TRAIL susceptibility is well documented in normal T cells as well as in individual leukemic cell samples. 18,40 To determine whether the expression pattern of TRAIL receptors R1-R4 might explain the rather low TRAIL susceptibility observed, we examined constitutive mRNA levels of these receptors by semi-quantitative RT-PCR.…”

“…34,35 To investigate TRAIL-mediated effects, leukemic cells were coincubated with 1 g/ml of soluble, recombinant, human TRAIL (N-terminally tagged with the FLAG epitope; Alexis, San Diego, CA, USA) and trimerized with a FLAG-specific antibody (2 g/ml; Alexis) as described elsewhere. 13 To assess a possible sensitization to TRAIL-induced apoptosis of leukemic cells by the chemotherapeutic agent doxorubicin (Pharmacia & Upjohn, Erlangen, Germany), cells were coincubated with doxorubicin at different concentrations (0.5, 2.5 and 12.5 g/ml) as well as with both TRAIL and doxorubicin, following the above described procedure.…”

Chemotherapeutic drugs sensitize pre-B ALL cells for CD95- and cytotoxic T-lymphocyte-mediated apoptosis

“…6 The 48 kDa CD95 surface antigen can mediate apoptosis upon crosslinking with monoclonal antibodies (anti-Fas, anti-APO-1) or natural cognate CD95-L. [7][8][9] Many cell types, both normal and malignant cells, express CD95. [10][11][12][13][14][15] While some T-and B-lineage malignancies are sensitive to CD95 triggering, the majority of primary leukemias are resistant towards CD95-mediated apoptosis. 8,15,16 Triggering of the T cell receptor in peripheral T cells leads to activation-induced cell death via CD95/CD95-L interaction.…”

“…[10][11][12][13][14][15] While some T-and B-lineage malignancies are sensitive to CD95 triggering, the majority of primary leukemias are resistant towards CD95-mediated apoptosis. 8,15,16 Triggering of the T cell receptor in peripheral T cells leads to activation-induced cell death via CD95/CD95-L interaction. 17 Similarly, antigen-activation in B cells leads to upregulation of CD95 and sensitivity towards CD95-induced apoptosis.…”