ArticleBlood2010
A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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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
66 citing papers in PubMed, 131 citations in OpenAlex.
- Pyridopyrimidines and Pyridopyrimidinones as Kinase-Targeted Anticancer Agents: Medicinal Chemistry and Mechanistic Insights.Molecules (Basel, Switzerland) · 2026Review
- NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation.Cancer medicine · 2024Article
- Review
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- Review
- PIM3-AMPK-HDAC4/5 axis restricts MuERVL-marked 2-cell-like state in embryonic stem cells.Stem cell reports · 2022Article
- Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy.PLoS neglected tropical diseases · 2022Article
- Synthesis of 2-Oxoquinoline Derivatives as Dual Pim and mTORC Protein Kinase Inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- Article
- Engineered Fully Human Single-Chain Monoclonal Antibodies to PIM2 Kinase.Molecules (Basel, Switzerland) · 2021Article
- PIM Kinases in Multiple Myeloma.Cancers · 2021Review
- Antiplatelet properties of Pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling.Haematologica · 2021Article
- T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies.Blood cancer discovery · 2021Review
- Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics.Journal of Cancer · 2021Review
- PIM Kinase Inhibitors Block the Growth of Primary T-cell Acute Lymphoblastic Leukemia: Resistance Pathways Identified by Network Modeling Analysis.Molecular cancer therapeutics · 2020Article
- Article
- Comparative acetylome analysis reveals the potential roles of lysine acetylation for DON biosynthesis in Fusarium graminearum.BMC genomics · 2019Article
- PIM kinase inhibitor, AZD1208, inhibits protein translation and induces autophagy in primary chronic lymphocytic leukemia cells.Oncotarget · 2019Article
- Pre-clinical evaluation of second generation PIM inhibitors for the treatment of T-cell acute lymphoblastic leukemia and lymphoma.Haematologica · 2019Article
- Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade.Cancer letters · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. In immunodeficient mice carrying subcutaneous pre-T-LBL tumors, treatment twice daily with SMI-4a caused a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries. Our data suggest that inhibition of the Pim protein kinases may be developed as a therapeutic strategy for the treatment of pre-T-LBL.
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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.