ArticleOncogene2002
Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 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
119 citing papers in PubMed, 281 citations in OpenAlex.
- Allogeneic hematopoietic stem cell transplantation at the first remission for younger adults with FLT3-internal tandem duplication AML: The JALSG AML209-FLT3-SCT study.Cancer science · 2020Trial
- Trial
- Treatment sequence with gilteritinib and allogeneic haematopoietic stem cell transplantation in relapsed/refractory FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukaemia patients: A multicentre real-world study.British journal of haematology · 2026Article
- Adaptor-mediated rewiring of FLT3 signaling engages p38 MAPK to sustain gilteritinib resistance in acute myeloid leukemia.Leukemia · 2026Article
- The type I FLT3 inhibitor XL999 overrides secondary FLT3-ITD mutations that arise under gilteritinib and quizartinib treatment in acute myeloid leukemia.Molecular biomedicine · 2026Article
- Review
- P300/CBP inhibition with inobrodib in combination with gilteritinib and venetoclax targets leukemia stem cells in epigenetic mutant AML.Science advances · 2026Article
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Review
- Recent Advancement in Drug Designing as Small Molecules in Targeted Cancer Therapy: Challenges and Future Directions.Current cancer drug targets · 2025Review
- Age-associated myeloid malignancies - the role of STAT3 and STAT5 in myelodysplastic syndrome and acute myeloid leukemia.FEBS letters · 2024Review
- DistinctInternational journal of molecular sciences · 2024Article
- Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Venetoclax therapy and emerging resistance mechanisms in acute myeloid leukaemia.Cell death & disease · 2024Review
- FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia.Leukemia · 2024Article
- Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia.NPJ precision oncology · 2023Article
- Optimization of Tyrosine Kinase Inhibitor-Loaded Gold Nanoparticles for Stimuli-Triggered Antileukemic Drug Release.Journal of functional biomaterials · 2023Article
- The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors.Cell death discovery · 2023Article
- Targeting Proliferation Signals and the Cell Cycle Machinery in Acute Leukemias: Novel Molecules on the Horizon.Molecules (Basel, Switzerland) · 2023Review
- Article
59 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
5 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Internal tandem duplication (ITD) of the juxtamembrane (JM) domain of FLT3 is the most frequent mutation in human acute myeloid leukemia, and is significantly associated with leukocytosis and a poor prognosis. Previously we reported that FLT3 with ITD (FLT3/ITD) formed a homodimer and was autophosphorylated on tyrosine residues, while the mechanism remains unclear. In this study, we elucidated the role of the JM domain in FLT3 activation. Mutant FLT3 with not only ITD but also an elongating or shortening JM domain transformed murine IL3-dependent myeloid progenitor cell line 32D regardless of the tyrosine residues in the JM domain. These mutant FLT3s were constitutively tyrosine phosphorylated and activated signal-transduction molecules such as SHC, MAP kinase and STAT5a. Notably, co-transfection of the truncated FLT3/ITD lacking kinase and C-terminal domains with the wild type (Wt)-FLT3 into 32D cells resulted in the autonomous proliferation. In these cells, truncated FLT3/ITD generated a hetero-complex with Wt-FLT3 and Wt-FLT3 was constitutively tyrosine phosphorylated. These findings indicate that the FLT3 JM domain plays an important role in receptor activation, and that the length-mutated JM domain induces ligand-independent receptor activation but also activates Wt-FLT3 in a trans-manner.
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.