ArticleThe Journal of clinical investigation2004
FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 168 citations in OpenAlex.
- Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.The Journal of experimental medicine · 2014Trial
- Trial
- Interstitial 11q Deletions and Terminal 11q Duplications Cause a Bleeding Tendency due to Platelet Dysfunction That Is Similar to 11q Deletions Causing Jacobsen Syndrome.European journal of haematology · 2026Article
- Molecular diagnosis of inherited platelet disorders: a tale of two realities - advanced vs. resource-limited setting.Thrombosis journal · 2025Review
- Heterozygous nonsenseResearch and practice in thrombosis and haemostasis · 2025Article
- Histone lysine methyltransferases MLL3 and MLL4 direct gene expression to produce platelets efficiently.Nature communications · 2025Article
- The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.International journal of molecular sciences · 2025Review
- Hematological abnormalities in Jacobsen syndrome: cytopenia of varying severities and morphological abnormalities in peripheral blood and bone marrow.Haematologica · 2023Article
- Sorting nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes.Haematologica · 2022Article
- Current insights into the role of Fli-1 in hematopoiesis and malignant transformation.Cellular and molecular life sciences : CMLS · 2022Review
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.Nature communications · 2021Article
- Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias.Journal of clinical medicine · 2021Review
- Inherited thrombocytopenias: history, advances and perspectives.Haematologica · 2020Review
- Genetic classification and confirmation of inherited platelet disorders: current status in Korea.Clinical and experimental pediatrics · 2020Article
- Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease.Vascular biology (Bristol, England) · 2020Article
- New Insights Into the Differentiation of Megakaryocytes From Hematopoietic Progenitors.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Downregulation ofOncotarget · 2019Article
- Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting.PLoS genetics · 2019Article
- Inherited Macrothrombocytopenia: Correlating Morphology, Epidemiology, Molecular Pathology and Clinical Features.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2018Review
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10 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paris-Trousseau syndrome (PTS; also known as Jacobsen syndrome) is characterized by several congenital anomalies including a dysmegakaryopoiesis with two morphologically distinct populations of megakaryocytes (MKs). PTS patients harbor deletions on the long arm of chromosome 11, including the FLI1 gene, which encodes a transcription factor essential for megakaryopoiesis. We show here that lentivirus-mediated overexpression of FLI1 in patient CD34(+) cells restores the megakaryopoiesis in vitro, indicating that FLI1 hemizygous deletion contributes to the PTS hematopoietic defects. FISH analysis on pre-mRNA and single-cell RT-PCR revealed that FLI1 expression is mainly monoallelic in CD41(+)CD42(-) progenitors, while it is predominantly biallelic in the other stages of megakaryopoiesis. In PTS cells, the hemizygous deletion of FLI1 generates a subpopulation of CD41(+)CD42(-) cells completely lacking FLI1 transcription. We propose that the absence of FLI1 expression in these CD41(+)CD42(-) cells might prevent their differentiation, which could explain the segregation of the PTS MKs into two subpopulations: one normal and one composed of small immature MKs undergoing a massive lysis, presumably originating from either FLI1(+) or FLI1(-) CD41(+)CD42(-) cells, respectively. Thus, we point to the role of transient monoallelic expression of a gene essential for differentiation in the genesis of human haploinsufficiency-associated disease and suggest that such a mechanism may be involved in the pathogenesis of other congenital or acquired genetic diseases.
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