ArticleBlood2020
13q12.2 deletions in acute lymphoblastic leukemia lead to upregulation of FLT3 through enhancer hijacking.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Fully exploiting SNP arrays: a systematic review on the tools to extract underlying genomic structure.Briefings in bioinformatics · 2022Pooled it
- Ptpn1 deficiency collaborates with a NUP98::HOXD13 fusion gene to generate B cell precursor acute lymphoblastic leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- Article
- The landscape of structural variation in pediatric cancer.Cancer cell · 2026Article
- Mechanisms of enhancer-driven oncogene activation.International journal of cancer · 2026Review
- FLT3: A 35-Year Voyage from Discovery to the Next Generation of Targeted Therapy in AML.Cancers · 2025Review
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Novel mutations of SRPX facilitate the stemness and malignant progression of glioma.British journal of cancer · 2025Article
- The landscape of structural variation in pediatric cancer.bioRxiv : the preprint server for biology · 2025Article
- Atypical B-Cell Acute Lymphoblastic Leukemia with iAMP21 in the Context of Constitutional Ring Chromosome 21: A Case Report and Review of the Genetic Insights.International journal of molecular sciences · 2025Review
- DNA regulatory element cooperation and competition in transcription.BMB reports · 2024Review
- Unraveling the Genetic Heterogeneity of Acute Lymphoblastic Leukemia Based on NGS Applications.Cancers · 2024Review
- Characterizing the allele-specific gene expression landscape in high hyperdiploid acute lymphoblastic leukemia with BASE.Scientific reports · 2024Article
- Oncogenic Enhancers in Leukemia.Blood cancer discovery · 2024Review
- Developmental origins shape the paediatric cancer genome.Nature reviews. Cancer · 2024Review
- Characterisation of FLT3 alterations in childhood acute lymphoblastic leukaemia.British journal of cancer · 2024Article
- Cancer Evolution: A Multifaceted Affair.Cancer discovery · 2024Article
- Prevalence ofFrontiers in pediatrics · 2024Article
- Spatial promoter-enhancer hubs in cancer: organization, regulation, and function.Trends in cancer · 2023Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the phosphatidylinositol 3-kinase/AKT-, RAS/MAPK-, and STAT5-signaling pathways. In this study, we examine the pathogenetic impact of somatic hemizygous 13q12.2 microdeletions in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) using 5 different patient cohorts (in total including 1418 cases). The 13q12.2 deletions occur immediately 5' of FLT3 and involve the PAN3 locus. By detailed analysis of the 13q12.2 segment, we show that the deletions lead to loss of a topologically associating domain border and an enhancer of FLT3. This results in increased cis interactions between the FLT3 promoter and another enhancer located distally to the deletion breakpoints, with subsequent allele-specific upregulation of FLT3 expression, expected to lead to ligand-independent activation of the receptor and downstream signaling. The 13q12.2 deletions are highly enriched in the high-hyperdiploid BCP ALL subtype (frequency 3.9% vs 0.5% in other BCP ALL) and in cases that subsequently relapsed. Taken together, our study describes a novel mechanism of FLT3 involvement in leukemogenesis by upregulation via chromatin remodeling and enhancer hijacking. These data further emphasize the role of FLT3 as a driver gene in BCP ALL.
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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.