ArticlePloS one2013
FLT3 mutations in early T-cell precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 106 citations in OpenAlex.
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- Cytogenetic and molecular characterization of an atypical ETP-ALL case with BCL2 dependency: therapeutic implications for Venetoclax use.Molecular biology reports · 2025Article
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- T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments.Leukemia · 2025Review
- Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia.Leukemia · 2025Article
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- Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.PNAS nexus · 2024Article
- [Chinese expert consensus on diagnosis and treatment of adult early T cell precursor acute lymphoblastic leukemia (2023)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Therapeutic Targeting of MERTK and BCL-2 in T-Cell and Early T-Precursor Acute Lymphoblastic Leukemia.Cancers · 2022Article
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- Broad genomic workup including optical genome mapping uncovers aFrontiers in oncology · 2022Article
- Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick.Biomarker research · 2021Review
- Redefining the biological basis of lineage-ambiguous leukemia through genomics: BCL11B deregulation in acute leukemias of ambiguous lineage.Best practice & research. Clinical haematology · 2021Review
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- A New Treatment Strategy for Early T-Cell Precursor Acute Lymphoblastic Leukemia: A Case Report and Literature Review.OncoTargets and therapy · 2021Article
- Early T-Cell Precursor Acute Lymphoblastic Leukemia: Diagnosis, Updates in Molecular Pathogenesis, Management, and Novel Therapies.Frontiers in oncology · 2021Review
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.
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