In:
Blood, American Society of Hematology, Vol. 91, No. 7 ( 1998-04-01), p. 2415-2422
Abstract:
The p210bcr-abl protein was shown to inhibit apoptosis induced by DNA damaging agents. Apoptotic DNA fragmentation is delayed in the bcr-abl+ K562 and KCL-22 compared with thebcr-abl− U937 and HL-60 cell lines when treated with etoposide concentrations that induce similar DNA damage in the four cell lines. By the use of a cell-free system, we show that nuclei from untreated cells that express p210bcr-abl remain sensitive to apoptotic DNA fragmentation induced by triton-soluble extracts from p210bcr-abl− cells treated with etoposide. In the four tested cell lines, apoptotic DNA fragmentation is associated with a decreased expression of procaspase-3 (CPP32/Yama/apopain) and its cleavage into a p17 active fragment, whereas the long isoform of procaspase-2 (ICH-1L) remains unchanged and the poly(adenosine diphosphate–ribose)polymerase protein is cleaved. These events are delayed in bcr-abl+ compared with bcr-abl− cell lines. The role of p210bcr-abl in this delay is confirmed by comparing the effect of etoposide on the granulocyte-macrophage colony-stimulating factor (GM-CSF)–dependent UT7 cells and thebcr-abl–transfected GM-CSF–independent UT7/9 clone. We conclude that the cytosolic pathway that leads to apoptotic DNA fragmentation in etoposide-treated leukemic cells is delayed upstream of procaspase-3–mediated events in bcr-abl+ cell lines.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V91.7.2415.2415_2415_2422
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1998
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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