ArticleThe Journal of experimental medicine2016
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics.Frontiers in oncology · 2020Pooled it
- Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells.Nature communications · 2026Article
- Alcohol consumption exacerbates high-fat diet-mediated disruptions in myelopoiesis and osteoclastogenesis in mouse models of metabolic dysfunction-associated liver diseases.Frontiers in endocrinology · 2026Article
- RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Absence of pre-transplant T cell response against LAA is associated with Flt3-ITD mutation and increased relapse-risk in AML patients with HSCT.Immunotherapy · 2025Article
- The interaction between common genetic mutations in AML and the immune landscape: mechanisms and implications for immune response.Frontiers in immunology · 2025Review
- Identification and validation of three tumor suppressors associated with the immune response of acute myeloid leukemia.Frontiers in genetics · 2025Article
- Biology of post-transplant relapse: actionable features.Hematology. American Society of Hematology. Education Program · 2024Review
- Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses.Nature communications · 2024Article
- Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation.Science immunology · 2024Article
- Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance.Experimental hematology & oncology · 2024Review
- Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect.Frontiers in immunology · 2024Review
- Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency.Frontiers in immunology · 2024Article
- Research Progress of Dendritic Cell Surface Receptors and Targeting.Biomedicines · 2023Review
- How ITD Insertion Sites Orchestrate the Biology and Disease of FLT3-ITD-Mutated Acute Myeloid Leukemia.Cancers · 2023Review
- Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells.Nature immunology · 2023Article
- Features of the TCR repertoire associate with patients' clinical and molecular characteristics in acute myeloid leukemia.Frontiers in immunology · 2023Article
- Review
- A novel insight into the pathophysiology of autoimmune hepatitis: An immune activator mutation in the FLT3 receptor.Hepatology forum · 2021Article
- Human CD141Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner.
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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.