Marked apoptosis of human myelomonocytic leukemia cell line P39: significance of cellular differentiation.
Myelodysplastic syndrome (MDS)-derived leukemia cell line P39/Tsugane could be induced to apoptosis by a variety of agents including metabolic inhibitors, a calcium ionophore and differentiation-inducing agents. As evaluated by characteristic morphological changes and oligonucleosomal lengths DNA ladder, the levels of apoptosis in P39 cells induced by actinomycin D, or A23187, were far greater than in other myeloid lines examined in this study. When 22-oxa-1 alpha, 25(OH)2D3 (D3), dimethyl sulfoxide (DMSO) and all-trans retinoic acid (RA) were used as differentiation-inducers, varying degrees of apoptosis were seen. D3 induced monocytoid differentiation, but not apoptosis above the control level. On the other hand, RA induced profound apoptosis concomitant with the progressive expression of differentiation markers. Studies on morphology, functions and phenotypes of P39 cells exposed to differentiation inducers suggest that the incidence of apoptosis was not affected by the process of differentiation, but cells in the process of varying degrees of differentiation may die via apoptosis. Moreover, RA-treated P39 cells are unique in the simultaneous occurrence of profound apoptosis and differentiation. We propose that RA-treated P39 differentiation model is ideally suited for the study of MDS.
Anzai
N
N
Department of Medicine, Faculty of Medicine, Kyoto University, Japan.
Kawabata
H
H
Hirama
T
T
Masutani
H
H
Ohmori
M
M
Yoshida
Y
Y
Okuma
M
M
D017209:Apoptosis / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003609:Dactinomycin; D000001:Calcimycin; D014212:Tretinoin; D004121:Dimethyl Sulfoxide