Apoptosis in B-cell lymphomas and reactive lymphoid tissues always involves activation of caspase 3 as determined by a new in situ detection method.
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.
Dukers
Danny F
DF
Department of Pathology, VU Medical Centre Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Oudejans
Joost J
JJ
Vos
Wim
W
ten Berge
Rosita L
RL
Meijer
Chris J L M
CJ
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
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