Abstract |
In autologous bone marrow transplantation in patients with acute myeloid leukemia (AML), 4-hydroperoxycyclophosphamide (4-HC) is a commonly used ex vivo purging agent for leukemic blasts. In the present report, we demonstrate that exposure to high concentrations of 4-HC for 1 hour, as used in ex vivo bone marrow purging, produces internucleosomal DNA fragmentation characteristic of apoptosis, or programmed cell death (PCD), in human myeloid leukemia HL60 cells. Lower concentrations of 4-HC (10, 20, or 50 microM/L) failed to cause this effect, while higher concentrations (> or = 200 microM/L) produced random DNA fragmentation. 4-HC-mediated internucleosomal DNA fragmentation was associated with a marked induction in c-jun and significant reductions in bcl-2 and c-myc oncogene expressions. A combined treatment with interleukin-3 (IL-3) plus IL-6 for 18 hours before an additional, 1-hour concurrent treatment with 4-HC (100 microM/L) significantly increased 4-HC-induced DNA fragmentation as well as colony growth inhibition of HL60 cells. The effects of cotreatment with IL-3 plus IL-6 were also associated with a further, modest decrease in bcl-2 and c-myc and augmentation of c-jun expression. These findings highlight an alternative mechanism of 4-HC-induced leukemic cell death that can be potentially enhanced by cotreatment with IL-3 plus IL-6.
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Authors | G Bullock, C Tang, E Tourkina, A M Ibrado, J Lutzky, Y Huang, M E Mahoney, K Bhalla |
Journal | Experimental hematology
(Exp Hematol)
Vol. 21
Issue 13
Pg. 1640-7
(Dec 1993)
ISSN: 0301-472X [Print] Netherlands |
PMID | 8243566
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Neoplasm
- Interleukin-3
- Interleukin-6
- RNA, Neoplasm
- Cyclophosphamide
- perfosfamide
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Topics |
- Apoptosis
(drug effects)
- Blotting, Southern
- Bone Marrow Purging
- Cyclophosphamide
(administration & dosage, analogs & derivatives, pharmacology)
- DNA, Neoplasm
(metabolism)
- Gene Expression
- Genes, jun
- Genes, myc
- Humans
- Interleukin-3
(administration & dosage, pharmacology)
- Interleukin-6
(administration & dosage, pharmacology)
- Leukemia, Myeloid
(pathology)
- RNA, Neoplasm
(analysis)
- Tumor Cells, Cultured
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