bms-387032 and Leukemia--Prolymphocytic--T-Cell

bms-387032 has been researched along with Leukemia--Prolymphocytic--T-Cell* in 1 studies

Other Studies

1 other study(ies) available for bms-387032 and Leukemia--Prolymphocytic--T-Cell

Article	Year
Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling. Leukemia, 2018, Volume: 32, Issue:3 T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clinical trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clinical testing. Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Cell Cycle; Cell Line, Tumor; Chromosome Aberrations; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Gene Expression; Gene Expression Profiling; High-Throughput Screening Assays; Humans; Janus Kinases; Leukemia, Prolymphocytic, T-Cell; Male; Middle Aged; Molecular Targeted Therapy; Mutation; Oxazoles; Phenotype; Protein Kinase Inhibitors; STAT Transcription Factors; Thiazoles	2018

Article

Year

Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.

Leukemia, 2018, Volume: 32, Issue:3

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clinical trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clinical testing.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Cell Cycle; Cell Line, Tumor; Chromosome Aberrations; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Gene Expression; Gene Expression Profiling; High-Throughput Screening Assays; Humans; Janus Kinases; Leukemia, Prolymphocytic, T-Cell; Male; Middle Aged; Molecular Targeted Therapy; Mutation; Oxazoles; Phenotype; Protein Kinase Inhibitors; STAT Transcription Factors; Thiazoles

2018