ArticleLeukemia2022
Protein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Functional characterization of snoRNA-derived RNA (sdRNA) expression in healthy hematopoiesis and acute myeloid leukemia.Leukemia · 2026Article
- Clinical Significance of FLT3-ITD Variation Allele Frequency in Acute Myeloid Leukemia: A Multicenter Study.Hematological oncology · 2026Article
- SFRP2 drives aerobic glycolysis and tumor progression in ovarian cancer by transcriptional upregulation of PTK2B.Journal of translational medicine · 2026Article
- Overcoming vascular niche-mediated TKI resistance in acute myeloid leukemia through miR-126 inhibition.NPJ systems biology and applications · 2026Article
- Functional combination of resveratrol and midostaurin induces cytotoxicity to overcome acquired midostaurin resistance in FLT3-ITD expressing acute myeloid leukemia cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Exploring medicinal mechanism of baicalin in tumor microenvironment of melanoma via bioinformatic and in vitro study.Medical oncology (Northwood, London, England) · 2025Article
- Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC.Current gene therapy · 2025Article
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- Bayesian inference for identifying tumour-specific cancer dependencies through integration of ex-vivo drug response assays and drug-protein profiling.BMC bioinformatics · 2024Article
- Roles and inhibitors of FAK in cancer: current advances and future directions.Frontiers in pharmacology · 2024Review
- Identification of calcium metabolism related score associated with the poor outcome in papillary thyroid carcinoma.Frontiers in oncology · 2023Article
- Computational Tactics for Precision Cancer Network Biology.International journal of molecular sciences · 2022Review
- Proteomics in Acute Myeloid Leukemia: Current Applications in Precision Medicine and Targeted Immunotherapy.Technology in cancer research & treatmentReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FLT3 tyrosine kinase inhibitor (TKI) therapy evolved into a standard therapy in FLT3-mutated AML. TKI resistance, however, develops frequently with poor outcomes. We analyzed acquired TKI resistance in AML cell lines by multilayered proteome analyses. Leupaxin (LPXN), a regulator of cell migration and adhesion, was induced during early resistance development, alongside the tyrosine kinase PTK2B which phosphorylated LPXN. Resistant cells differed in cell adhesion and migration, indicating altered niche interactions. PTK2B and LPXN were highly expressed in leukemic stem cells in FLT3-ITD patients. PTK2B/FAK inhibition abrogated resistance-associated phenotypes, such as enhanced cell migration. Altered pathways in resistant cells, assessed by nascent proteomics, were largely reverted upon PTK2B/FAK inhibition. PTK2B/FAK inhibitors PF-431396 and defactinib synergized with different TKIs or daunorubicin in FLT3-mutated AML. Midostaurin-resistant and AML cells co-cultured with mesenchymal stroma cells responded particularly well to PTK2B/FAK inhibitor addition. Xenograft mouse models showed significant longer time to leukemia symptom-related endpoint upon gilteritinib/defactinib combination treatment in comparison to treatment with either drug alone. Our data suggest that the leupaxin-PTK2B axis plays an important role in acquired TKI resistance in AML. PTK2B/FAK inhibitors act synergistically with currently used therapeutics and may overcome emerging TKI resistance in FLT3-mutated AML at an early timepoint.
Indexed as
Identifiers
What OpenQuestion holds
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.