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The Notch ligand, Delta-1, alters retinoic acid (RA)-induced neutrophilic differentiation into monocytic and reduces RA-induced apoptosis in NB4 cells.

Murata-Ohsawa M, Tohda S, Kogoshi H, Sakano S, Nara N

Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan.

Effects of Notch activation on retinoic acid (RA)-induced differentiation and apoptosis were investigated. NB4, an acute promyelocytic leukemia (APL) cell line, undergoes neutrophilic differentiation and apoptosis by RA. Notch activation induced by a recombinant Notch ligand, Delta-1, did not affect the growth by itself. Treatment with RA plus Delta-1 made part of NB4 cells monocyte-like shaped and reduced the apoptosis. Similar phenomenon was also observed in primary APL cells. RA treatment induced cleavage of caspase-8 and PARP in NB4. Delta-1 suppressed the RA-induced cleavage of them, which may be a possible mechanism through which Delta-1 suppressed the RA-induced apoptosis.

Published 20 December 2004 in Leuk Res, 29(2): 197-203.
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