title: Apoptosis in B-cell lymphomas and reactive lymphoid tissues always involves activation of caspase 3 as determined by a new in situ detection method.
abstract: In vitro studies indicate that in lymphomas, execution of apoptosis involves activation of effector caspases. To investigate activation of effector caspases in vivo in biopsy specimens of lymphomas, a new assay was developed using antibodies against active caspase 3 and p89, a protein fragment generated by caspase-specific cleavage of poly-ADP ribose polymerase (PARP). Using this assay, it was found that in B-cell lymphomas, levels of active caspase 3/p89-positive cells correlate strongly with morphologically recognizable apoptotic cells. The number of active caspase 3/p89-positive cells was low in follicular lymphomas and usually high in diffuse large cell lymphomas. Highest numbers were found in Burkitt lymphomas and in two biopsies of diffuse large B-cell lymphomas (DLCLs) obtained several days after initiation of therapy. It is concluded that apoptosis in reactive lymphoid tissues and in B-cell lymphomas always involves activation of effector caspase 3 and cleavage of one of the major effector caspase substrates, PARP-1. Moreover, levels of effector caspase activation are constantly low in low-grade follicular lymphomas and vary considerably in DLCL and Burkitt lymphoma.
authors.affiliation: Department of Pathology, VU Medical Centre Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Danny F
authors.initials: DF
authors.lastname: Dukers
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: Wim
authors.initials: W
authors.lastname: Vos
authors.forename: Rosita L
authors.initials: RL
authors.lastname: ten Berge
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007244:Infectious Mononucleosis / Q000201:enzymology / Q000473:pathology*; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000201:enzymology / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000201:enzymology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000032:analysis; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D004792:Enzyme Precursors; D011506:Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases