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First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia.
- Source :
-
Blood . 12/7/2017, Vol. 130 Issue 23, p2499-2503. 5p. - Publication Year :
- 2017
-
Abstract
- T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with expression of the BCL-2 family members myeloid cell leukemia1(MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BCL-2 proteins
*T-cell lymphoma
*LEUKEMIA
*ACUTE myeloid leukemia
Subjects
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 130
- Issue :
- 23
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 126618307
- Full Text :
- https://doi.org/10.1182/blood-2017-05-785683