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Rescue from programmed cell death in leukemic and normal myeloid cells
J Lotem, EJ Cragoe and L Sachs
Department of Molecular Genetics and Virology, Weizmann Institute of
Science, Rehovot, Israel.
Growth factor-independent clones of myeloid leukemic cells can regain a
growth factor-dependent state during differentiation. Loss of viability in
these differentiating leukemic cells in the absence of growth factor was
associated with DNA fragmentation and morphologic changes typical of
programmed cell death (apoptosis). The differentiating leukemic cells could
be rescued from apoptosis by a hematopoietic growth factor such as
interleukin-3 (IL-3) and by the tumor-promoting phorbol ester
12-O-tetra-decanoyl-phorbol-13-acetate (TPA), but not by the nonpromoting
phorbol ester 4-alpha-TPA. IL-3 and TPA rescued differentiating myeloid
leukemic cells by different pathways and also rescued normal myeloid
precursor cells from apoptosis. The rescue of differentiating leukemic and
normal myeloid cells by IL-3 or TPA was blocked by amiloride inhibitors of
the Na+/H+ antiporter. We suggest that TPA may act as a tumor promoter by
inhibiting programmed cell death.
Volume 78,
Issue 4,
pp. 953-960,
08/15/1991
Copyright © 1991 by The American Society of Hematology
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