ArticleBlood2019
NPM1c alters FLT3-D835Y localization and signaling in acute myeloid leukemia.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- FLT3-TKD in the prognosis of patients with acute myeloid leukemia: A meta-analysis.Frontiers in oncology · 2023Pooled it
- Article
- Impact of FLT3 mutation on its intracellular localization and implications for anti-leukemia strategy.Annals of hematology · 2025Review
- Review
- Importance of PTM of FLT3 in acute myeloid leukemia.Acta biochimica et biophysica Sinica · 2024Review
- BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia.Cancer science · 2024Article
- NIPA (Nuclear Interaction Partner of ALK) Is Crucial for Effective NPM-ALK Mediated Lymphomagenesis.Frontiers in oncology · 2022Article
- Review
- FLT3-ITD transduces autonomous growth signals during its biosynthetic trafficking in acute myelogenous leukemia cells.Scientific reports · 2021Article
- Menin inhibition decreases Bcl-2 and synergizes with venetoclax in NPM1/FLT3-mutated AML.Blood · 2021Article
- The Ups and Downs of STAT Inhibition in Acute Myeloid Leukemia.Biomedicines · 2021Review
- Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.Experimental hematology & oncology · 2021Article
- Article
- Clinical implications of recurrent gene mutations in acute myeloid leukemia.Experimental hematology & oncology · 2020Review
- Mutations of FLT3 receptor affect its surface glycosylation, intracellular localization, and downstream signaling.Leukemia research reports · 2020Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Activating mutations in FMS-like tyrosine kinase receptor-3 (FLT3) and Nucleophosmin-1 (NPM1) are most frequent alterations in acute myeloid leukemia (AML), and are often coincidental. The mutational status of NPM1 has strong prognostic relevance to patients with point mutations of the FLT3 tyrosine kinase domain (TKD), but the biological mechanism underlying this effect remains unclear. In the present study, we investigated the effect of the coincidence of NPM1c and FLT3-TKD. Although expression of FLT3-TKD is not sufficient to induce a disease in mice, coexpression with NPM1c rapidly leads to an aggressive myeloproliferative disease in mice with a latency of 31.5 days. Mechanistically, we could show that FLT3-TKD is able to activate the downstream effector molecule signal transducer and activator of transcription 5 (STAT5) exclusively in the presence of mutated NPM1c. Moreover, NPM1c alters the cellular localization of FLT3-TKD from the cell surface to the endoplasmic reticulum, which might thereby lead to the aberrant STAT5 activation. Importantly, aberrant STAT5 activation occurs not only in primary murine cells but also in patients with AML with combined FLT3-TKD and NPM1c mutations. Thus, our data indicate a new mechanism, how NPM1c mislocalizes FLT3-TKD and changes its signal transduction ability.
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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 Socratic graph.