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Blood, 15 July 2001, Vol. 98, No. 2, pp. 414-421
NEOPLASIA
Apaf-1 protein deficiency confers resistance to cytochrome
c-dependent apoptosis in human leukemic cells
Li Jia,
Srinivasa M. Srinivasula,
Feng-Ting Liu,
Adrian C. Newland,
Teresa Fernandes-Alnemri,
Emad
S. Alnemri, and
Stephen M. Kelsey
From the Department of Haematology, St Bartholomew's
and The Royal London School of Medicine and Dentistry, London, United
Kingdom; and the Department of Microbiology and Immunology, Kimmel
Cancer Institute, Thomas Jefferson University, Philadelphia, PA.
The human leukemia cell lines K562, CEM, CEM/VLB100,
human leukemic blasts, and the bladder cancer J82 cell line have
different sensitivities to UV light-induced apoptosis. It is reported
that resistance to UV light-induced apoptosis occurs at a point in the
apoptotic pathway upstream of caspase-3 but downstream of mitochondrial
cytochrome c release. It is demonstrated that the block is
due to deficiency of Apaf-1, a critical member of the apoptosome.
Sensitivity to apoptosis was independent of caspase-9b or XIAP
(inhibitors of apoptosis proteins) expression or levels of
procaspase-9. Transfection of Apaf-1 conferred sensitivity to apoptosis
in resistant cells. Apaf-1 deficiency may constitute a significant mode
of resistance to apoptosis in human leukemia.
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