ArticleExperimental hematology2014
Flk2/Flt3 promotes both myeloid and lymphoid development by expanding non-self-renewing multipotent hematopoietic progenitor cells.
Article in Experimental hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
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- 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
- Aging of hematopoietic stem cells is inconsequential to progenitor cell function.Stem cell reports · 2026Article
- Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Susceptibility in Adulthood.bioRxiv : the preprint server for biology · 2025Article
- Tracking Response and Resistance in Acute Myeloid Leukemia through Single-Cell DNA Sequencing Helps Uncover New Therapeutic Targets.International journal of molecular sciences · 2024Article
- Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions.The Journal of experimental medicine · 2024Article
- Hematopoietic stem cells and extramedullary hematopoiesis in the lungs.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023Review
- Lineage tracking to reveal the fate of hematopoietic stem cells influenced by Flk2Experimental & molecular medicine · 2023Article
- Prenatal inflammation perturbs murine fetal hematopoietic development and causes persistent changes to postnatal immunity.Cell reports · 2022Article
- Flt3 Signaling in B Lymphocyte Development and Humoral Immunity.International journal of molecular sciences · 2022Review
- IL7Rα, but not Flk2, is required for hematopoietic stem cell reconstitution of tissue-resident lymphoid cells.Development (Cambridge, England) · 2022Article
- New transgenic mouse models enabling pan-hematopoietic or selective hematopoietic stem cell depletion in vivo.Scientific reports · 2022Article
- Hydrogels Containing Gradients in Vascular Density Reveal Dose-Dependent Role of Angiocrine Cues on Stem Cell Behavior.Advanced functional materials · 2021Article
- CFU-S assay: a historical single-cell assay that offers modern insight into clonal hematopoiesis.Experimental hematology · 2021Review
- Evasion of the Host Immune Response by Betaherpesviruses.International journal of molecular sciences · 2021Review
- Megakaryocyte progenitor cell function is enhanced upon aging despite the functional decline of aged hematopoietic stem cells.Stem cell reports · 2021Article
- Potential targeting of FLT3 acute myeloid leukemia.Haematologica · 2021Review
- Human Cytomegalovirus UL7, miR-US5-1, and miR-UL112-3p Inactivation of FOXO3a Protects CD34mSphere · 2021Article
- Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells.Frontiers in microbiology · 2021Review
- Dasatinib overcomes stroma-based resistance to the FLT3 inhibitor quizartinib using multiple mechanisms.Leukemia · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Defining differentiation pathways is central to understanding the pathogenesis of hematopoietic disorders, including leukemia. The function of the receptor tyrosine kinase Flk2 (Flt3) in promoting myeloid development remains poorly defined, despite being commonly mutated in acute myeloid leukemia. We investigated the effect of Flk2 deficiency on myelopoiesis, focusing on specification of progenitors between HSC and mature cells. We provide evidence that Flk2 is critical for proliferative expansion of multipotent progenitors that are common precursors for all lymphoid and myeloid lineages, including megakaryocyte/erythroid (MegE) cells. Flk2 deficiency impaired the generation of both lymphoid and myeloid progenitors by abrogating propagation of their common upstream precursor. At steady state, downstream compensatory mechanisms masked the effect of Flk2 deficiency on mature myeloid output, whereas transplantation of purified progenitors revealed impaired generation of all mature lineages. Flk2 deficiency did not affect lineage choice, thus dissociating the role of Flk2 in promoting cell expansion and regulating cell fate. Surprisingly, despite impairing myeloid development, Flk2 deficiency afforded protection against myeloablative insult. This survival advantage was attributed to reduced cell cycling and proliferation of progenitors in Flk2-deficient mice. Our data support the existence of a common Flk2(+) intermediate for all hematopoietic lineages and provide insight into how activating Flk2 mutations promote hematopoietic malignancy by non-Flk2-expressing myeloid cells.
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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.