PCNA Ki-67 dissociation in childhood acute lymphoblastic leukaemia. An immunofluorescent laser confocal scanning microscopical study.
Cell proliferation rates of diagnostic marrow aspirate cells of 21 children with Acute Lymphoblastic Leukaemia and 16 controls were compared using immunocytochemical labelling of PCNA and Ki-67 antigen as assessed by Confocal Laser Scanning Microscopy. The results showed an unexpected, highly significant degree of dissociation between PCNA and Ki-67 expression in ALL blasts. The PCNA labelling indices of ALL patients were significantly increased (mean 44, range 24-77) compared with normal reactive marrow cells (mean 13.8, range 4-26) (p < 0.000001, Mann Whitney U two tailed test), suggesting an abnormal commitment to proliferation. Ki-67 expression was raised to a lesser extent in ALL cells (mean 14.8, range 1.2-35) when compared to non-malignant proliferations (mean 6.6, range 1.7-25) (p < 0.02). PCNA/Ki-67 LI ratios in ALL (mean 7, range 1.1-35) were higher than in controls (mean 2.7, range 1.04-6.5, p < 0.09). As cell proliferation rates actually achieved in the bone marrow do not differ as strongly as suggested by the extreme difference in PCNA labelling, a pathological dissociation of PCNA/Ki-67 expression exists, suggesting immortalisation.
Ball
L M
LM
Dep. of Paediatric Clinical Haematology, RLCH Alder Hey, United Kingdom.
Pope
J
J
Howard
C V
CV
Eccles
P
P
van Velzen
D
D
D000293:Adolescent; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000737:chemistry*; D002453:Cell Cycle; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen; D008297:Male; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*
D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen