ArticleLeukemia2012
Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- FLT3: A 35-Year Voyage from Discovery to the Next Generation of Targeted Therapy in AML.Cancers · 2025Review
- Prognostic Factors, FLT-3 Mutations, and Treatment Outcomes with Pediatric-Inspired Protocols in Adolescent and Young Adults and Adult Patients with Acute Lymphoblastic Leukemia.Acta haematologica · 2025Article
- DistinctInternational journal of molecular sciences · 2024Article
- Characterisation of FLT3 alterations in childhood acute lymphoblastic leukaemia.British journal of cancer · 2024Article
- Prevalence ofFrontiers in pediatrics · 2024Article
- Case Report: RareGenes · 2023Article
- Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia.Molecular oncology · 2022Article
- A novel IgG-based FLT3xCD3 bispecific antibody for the treatment of AML and B-ALL.Journal for immunotherapy of cancer · 2022Article
- Tyrosine kinases in KMT2A/MLL-rearranged acute leukemias as potential therapeutic targets to overcome cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- Does lineage plasticity enable escape from CAR-T cell therapy? Lessons from MLL-r leukemia.Experimental hematology · 2021Review
- Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLL-rearranged B cell acute lymphoblastic leukemia.The Journal of clinical investigation · 2021Article
- Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2021Review
- Review
- Article
- Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? When? Why?Biomarker research · 2020Review
- MLL-Rearranged Acute Lymphoblastic Leukemia.Current hematologic malignancy reports · 2020Review
- Induction of NK Cell Reactivity against B-Cell Acute Lymphoblastic Leukemia by an Fc-Optimized FLT3 Antibody.Cancers · 2019Article
- Review
- Unraveling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic leukemia using genome-wide analysis.Haematologica · 2019Article
- Next-Generation Evaluation and Treatment of Pediatric Acute Lymphoblastic Leukemia.The Journal of pediatrics · 2018Review
Corrections and comments
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Authors and funding
18 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL (n=49) or T-ALL (n=5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1+ B-ALL overexpressed FLT3. In contrast, mainly MLL-AF4+ B-ALL but also ETV6-RUNX1+, BCR-ABL+ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3, rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P=0.002) and disease-free survival (DFS; 0 vs 43%; P=0.03) in MLL-AF4+ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age>14 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4+ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4+ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.
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