ArticleLeukemia2018
Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Advances and Perspectives in the Treatment of T-PLL.Current hematologic malignancy reports · 2020Pooled it
- Single-cell genomics highlight MYC-associated metabolic activation and altered cell interactions in T-prolymphocytic leukemia progression.Nature communications · 2026Article
- Multiomics Profiling of T-cell Leukemia and Lymphoma Enables Targeted Therapeutic Discovery.Cancer research · 2026Article
- Comparative preclinical drug response analyses of T-prolymphocytic leukemia reveal no differences between known gene expression subgroups.Biology direct · 2025Article
- Dual STAT3/STAT5 inhibition as a novel treatment strategy in T-prolymphocytic leukemia.Leukemia · 2025Article
- Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Prolymphocytic Leukemia.Journal of clinical medicine · 2025Article
- T-cell prolymphocytic leukemia, a case report and review of the literature.Oncology research · 2025Review
- Proteasome Inhibitors Induce Apoptosis in Ex Vivo Cells of T-Cell Prolymphocytic Leukemia.International journal of molecular sciences · 2024Article
- Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.HemaSphere · 2024Article
- Recent advances in and applications of ex vivo drug sensitivity analysis for blood cancers.Blood research · 2024Review
- Review
- Prolymphocytic Leukaemia: an Update on Biology and Treatment.Current oncology reports · 2024Review
- T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment.International journal of molecular sciences · 2023Review
- Sensitivity of canine hematological cancers to BH3 mimetics.Journal of veterinary internal medicine · 2023Article
- Article
- Article
- All that glitters is not LGL Leukemia.Leukemia · 2022Review
- Precision oncology using ex vivo technology: a step towards individualised cancer care?Expert reviews in molecular medicine · 2022Review
- Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research.Transplantation and cellular therapy · 2022Article
- Deregulation of JAK2 signaling underlies primary cutaneous CD8Haematologica · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 11 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.