ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Hoxa9 regulates Flt3 in lymphohematopoietic progenitors.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Unlocking the HOX: Homeobox Genes as Regulators of Hematopoietic Development.International journal of molecular sciences · 2026Review
- Article
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Pan-cancer exploration of oncogenic and clinical impacts revealed that HOXA9 is a diagnostic indicator of tumorigenesis.Clinical and experimental medicine · 2024Article
- HOXA9 transcription factor is a double-edged sword: from development to cancer progression.Cancer metastasis reviews · 2024Review
- HOXA9 Regulome and Pharmacological Interventions in Leukemia.Advances in experimental medicine and biology · 2024Review
- Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens.Nature communications · 2023Article
- Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential.Cancer cell international · 2022Review
- Flt3 Signaling in B Lymphocyte Development and Humoral Immunity.International journal of molecular sciences · 2022Review
- Article
- DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia.Environment international · 2019Article
- Combination of ATO with FLT3 TKIs eliminates FLT3/ITD+ leukemia cells through reduced expression of FLT3.Oncotarget · 2018Article
- Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis.Leukemia · 2017Article
- Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.PLoS computational biology · 2016Article
- Review
- The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by stimulating IL-1β and NF-κB signaling.Journal of cell science · 2015Article
- Cell extrinsic alterations in splenic B cell maturation in Flt3-ligand knockout mice.Immunity, inflammation and disease · 2015Article
- Toll-like receptor 9 and interferon-γ receptor signaling suppress the B-cell fate of uncommitted progenitors in mice.European journal of immunology · 2015Article
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Early B cell factor (EBF) is a transcription factor essential for specification and commitment to the B cell fate. In this study, we show downregulation of a developmentally regulated cluster of hoxa genes, notably hoxa9, coincides with induction of EBF at the Pro-B cell stage of B cell differentiation. Analysis of the hematopoietic progenitor compartment in Hoxa9(-/-) mice revealed significantly reduced frequencies and expression levels of Flt3, a cytokine receptor important for lymphoid priming and the generation of B cell precursors (BCPs). We show that Hoxa9 directly regulates the flt3 gene. Chromatin immunoprecipitation analysis revealed binding of Hoxa9 to the flt3 promoter in a lymphoid progenitor cell line. Knockdown of Hoxa9 significantly reduced Flt3 transcription and expression. Conversely, forced expression of Hoxa9 increased Flt3 transcription and expression in a Pro-B cell line that expressed low levels of Flt3. Hoxa9 inversely correlated with ebf1 in ex vivo-isolated bone marrow progenitors and BCPs, suggesting that EBF might function to silence a Hoxa9 transcriptional program. Restoration of EBF function in an EBF(-/-) cell line induced B lineage gene expression but did not directly suppress hoxa9 transcription, revealing alternate mechanisms of Hoxa9 regulation in BCPs. These data provide new insight into Hoxa9 function and regulation during lymphoid and B cell development. Furthermore, they suggest that failure to upregulate Flt3 provides a molecular basis for the lymphoid/early B cell deficiencies in Hoxa9(-/-) mice.
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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.