T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of T-cell precursors and is being studied as a disease model and treatment target for apoptosis-based therapy and immunotherapy. It shows heterogeneous sensitivity to BH3-mimetics and NK cell-mediated killing, highlighting variable anti-apoptotic dependencies across samples. BH3-profiling was used to assess these dependencies in T-ALL, supporting functional classification of survival pathways rather than relying on genotype alone. Therapeutic evaluation included BCL-2 inhibition with venetoclax, BCL-XL inhibition with a1331852, dual BCL-2/BCL-XL inhibition with azd4320, and MCL-1 inhibition with azd5991. Overall, the literature positions T-ALL as a context for testing how apoptosis-targeting agents and natural killer cells-based cytotoxicity can be leveraged against a highly heterogeneous leukemia.
Apoptosis-targeted therapy
- BH3-profiling was used to assess anti-apoptotic dependencies in T-ALL samples, providing a functional readout for BH3-mimetic sensitivity. (PMID:41935056)
- BCL-2 inhibition with venetoclax was evaluated in T-ALL in the context of BH3-mimetic therapy. (PMID:41935056)
- BCL-XL inhibition with a1331852 was evaluated in T-ALL. (PMID:41935056)
- Dual BCL-2/BCL-XL inhibition with azd4320 and MCL-1 inhibition with azd5991 were also tested in T-ALL. (PMID:41935056)
Immunotherapy
- NK cell-mediated killing was investigated in T-ALL as a potential immunotherapeutic approach. (PMID:41935056)
- The disease showed heterogeneous sensitivity to natural killer cells-mediated killing, indicating variable susceptibility among T-ALL samples. (PMID:41935056)
- The 2026 Cell Death & Disease study framed T-ALL as a setting for combining BH3-mimetics with NK cell-mediated immunotherapy. (PMID:41935056)