Abstract
With the advent of proteasome inhibitors (bortezomib) and pleiotropic pathway modulators which target cereblon E3 ligase (lenalidomide), the ubiquitin-proteasome system has emerged as a tractable target in non-Hodgkin lymphoma and multiple myeloma. Here we report that TAK-243, a small molecule inhibitor of the ubiquitin-activating enzyme (UAE), induced ER stress and the unfolded protein response in primary chronic lymphocytic leukemia cells, facilitating cell death. Moreover, targeting UAE was effective in ibrutinib-resistant mantle cell lymphoma cell lines and primary cells in vitro. Thus, UAE is a promising target in lymphoid malignancies, including ibrutinib-resistant lymphomas, an area of unmet medical need.
Original language | English (US) |
---|---|
Pages (from-to) | 2946-2950 |
Number of pages | 5 |
Journal | Leukemia and Lymphoma |
Volume | 60 |
Issue number | 12 |
DOIs | |
State | Published - Oct 15 2019 |
Keywords
- CLL
- TAK-243
- Ubiquitin-activating enzyme
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research