Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
The University of Texas MD Anderson Cancer Center · Harvard University · +6 more institutions
Abstract
Abstract B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover,…
Citation impact
- FWCI
- 18.94
- Percentile
- 100%
- References
- 34
Authors
32- RPRongqing Pan
The University of Texas MD Anderson Cancer Center, Harvard University, University of California, San Francisco, AbbVie (United States), Munich Leukemia Laboratory (Germany), Dana-Farber Cancer Institute, University Hospital Ulm, The Ohio State University
- LJLeah J. Hogdal
The University of Texas MD Anderson Cancer Center, Harvard University, University of California, San Francisco, AbbVie (United States), Munich Leukemia Laboratory (Germany), Dana-Farber Cancer Institute, University Hospital Ulm, The Ohio State University
- JMJuliana M. Benito
The University of Texas MD Anderson Cancer Center, Harvard University, University of California, San Francisco, AbbVie (United States), Munich Leukemia Laboratory (Germany), Dana-Farber Cancer Institute, University Hospital Ulm, The Ohio State University
- DBDonna Bucci
The University of Texas MD Anderson Cancer Center, Harvard University, University of California, San Francisco, AbbVie (United States), Munich Leukemia Laboratory (Germany), Dana-Farber Cancer Institute, University Hospital Ulm, The Ohio State University
- LHLina Han
The University of Texas MD Anderson Cancer Center, Harvard University, University of California, San Francisco, AbbVie (United States), Munich Leukemia Laboratory (Germany), Dana-Farber Cancer Institute, University Hospital Ulm, The Ohio State University
Topics & keywords
- Myeloid leukemia
- Leukemia
- Myeloid
- Ex vivo
- Cancer research
- Medicine
- Programmed cell death
- Chronic lymphocytic leukemia
- Good health and well-being