Expression of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors and sensitivity to trail-induced apoptosis in primary B-cell acute lymphoblastic leukaemia cells

• Published in: British journal of haematology Vol. 111; no. 2; pp. 580 - 586
• Main Authors: CLODI, Katharina, WIMMER, Doris, YANG LI, GOODWIN, Raymond, JAEGER, Ulrich, MANN, Georg, GADNER, Helmut, YOUNES, Anas
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.11.2000; Blackwell Publishing Ltd
• Subjects: Adolescent; Apoptosis; Apoptosis Regulatory Proteins; Biological and medical sciences; Blotting, Western - methods; Burkitt Lymphoma - drug therapy; Burkitt Lymphoma - metabolism; Carrier Proteins - metabolism; CASP8 and FADD-Like Apoptosis Regulating Protein; CD40 Ligand - metabolism; Child; Child, Preschool; fas Receptor; Female; GPI-Linked Proteins; Hematologic and hematopoietic diseases; Hematology; Humans; Infant; Intracellular Signaling Peptides and Proteins; Jurkat Cells; Ligands; Male; Medical sciences; Membrane Glycoproteins - therapeutic use; Platelet diseases and coagulopathies; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Member 10c; TNF-Related Apoptosis-Inducing Ligand; Tumor Cells, Cultured - drug effects; Tumor Necrosis Factor Decoy Receptors; Tumor Necrosis Factor-alpha - therapeutic use; Antineoplastic agent; Human; Acute; Precursor cell; Malignant hemopathy; B-Lymphocyte; In vitro; Biological activity; Lymphoproliferative syndrome; CD40 ligand; Acute lymphocytic leukemia; TNF related apoptosis; Tumor cell; Apoptosis; Biological receptor
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2000.02404.x

Because tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 ligand) preferentially kills malignant cells while sparing normal cells, it may be therapeutically useful against cancers, including those of haematopoietic origin. Although the activity of TRAIL has been studied in tumour cell lines and in a limited number of different primary tumours, its overall activity in a large number of uniform cases of primary tumours is not known. We therefore studied the activity of TRAIL in 29 primary precursor B-cell acute lymphoblastic leukaemia (ALL) samples. TRAIL was found to have a modest activity as it killed a maximum of 29% of ALL cells within 18 h compared with killing 75% of Jurkat cells. The sensitivity to TRAIL did not correlate with the pattern of TRAIL receptor expression or FLIP expression, as determined by Western blot analysis. The CD40 receptor, which can transduce survival signals in mature malignant B cells, was less frequently expressed on ALL cells, but incubation with an exogenous soluble CD40 ligand trimer did not rescue them from spontaneous apoptosis and did not mediate their resistance to TRAIL. Further, although ALL cells expressed TRAIL protein, they failed to kill target Jurkat cells in a TRAIL-dependent manner. Our data delineate major biological differences between mature and precursor malignant B cells and suggest a limited therapeutic role for TRAIL as a single agent in primary B-cell ALL.