Abstract | BACKGROUND:
ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 to induce apoptosis in malignant cells and has shown promise as an effective anti-leukemic agent in pediatric preclinical tests. This study focuses on the effects of ABT-737 on leukemia cells with MLL rearrangement and identifies some of the biological correlates of its activity. PROCEDURE: Cells were cultured in the presence of increasing concentrations of ABT-737 alone or in combination with other agents. After 4 days in culture, cell growth inhibition was measured by Alamar blue assay. The expression and activation of potential intracellular targets of ABT-737 activity were determined by Western blot analysis. RESULTS: CONCLUSIONS: We describe the in vitro studies to demonstrate the activity and drug combinability of ABT-737 against MLL rearranged leukemia cells. In addition, identification of the molecular changes that occur in the presence of ABT-737 provides information regarding effective target validation and target modulation analyses in future clinical trials.
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Authors | Aarthi Jayanthan, Andrea Incoronato, Anjali Singh, Christopher Blackmore, Delphine Bernoux, Victor Lewis, Ronald Stam, James A Whitlock, Aru Narendran |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 56
Issue 3
Pg. 353-60
(Mar 2011)
ISSN: 1545-5017 [Electronic] United States |
PMID | 21225911
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Wiley-Liss, Inc. |
Chemical References |
- ABT-737
- Antineoplastic Agents
- Biphenyl Compounds
- Drug Combinations
- KMT2A protein, human
- Nitrophenols
- Piperazines
- Proto-Oncogene Proteins c-bcl-2
- Sulfonamides
- Myeloid-Lymphoid Leukemia Protein
- Cytochromes c
- Histone-Lysine N-Methyltransferase
- Poly(ADP-ribose) Polymerases
- Caspase 8
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Biphenyl Compounds
(pharmacology)
- Blotting, Western
- Caspase 8
(metabolism)
- Cell Line, Tumor
- Cytochromes c
(metabolism)
- Drug Combinations
- Gene Rearrangement
- Histone-Lysine N-Methyltransferase
- Humans
- Infant
- Male
- Myeloid-Lymphoid Leukemia Protein
(genetics)
- Nitrophenols
(pharmacology)
- Piperazines
(pharmacology)
- Poly(ADP-ribose) Polymerases
(metabolism)
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(drug therapy, genetics, pathology)
- Proto-Oncogene Proteins c-bcl-2
(antagonists & inhibitors, metabolism)
- Sulfonamides
(pharmacology)
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