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    1. A dual inhibitor overcomes drug-resistant FLT3-ITD acute myeloid leukemia

      [Paper-level Aggregated] PMCID: PMC8255005

      Evidence Type(s): Prognostic, Oncogenic, Functional

      Justification: Prognostic: The text states that FLT3 mutations are associated with poor prognosis in acute myeloid leukemia (AML), indicating that the presence of these mutations can provide information about the likely outcome of the disease. Oncogenic: The mention of FLT3 mutations, including D835 and F691L, as common genetic alterations in AML suggests that these variants contribute to the development of cancer. Functional: The text discusses the resistance of FLT3 mutations (specifically F691L and D835Y) to FLT3 inhibitors and the mechanisms by which KX2-391 overcomes this resistance, indicating a functional role of these mutations in drug response.

      Gene→Variant (gene-first): FLT3(2322):D835 FLT3(2322):D835Y FLT3(2322):F691 FLT3(2322):F691L

      Genes: FLT3(2322)

      Variants: D835 D835Y F691 F691L

    2. FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Multiple FLT3 inhibitors are in various stages of clinical evaluation. However

      [Paragraph-level] PMCID: PMC8255005 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the resistance of FLT3 mutations, specifically F691L, to FLT3 inhibitors and highlights the efficacy of KX2-391 in overcoming this resistance, indicating a correlation with treatment response. Oncogenic: The FLT3 mutations, including D835 and F691, are described as contributing to tumor development and progression in acute myeloid leukemia (AML), which supports their classification as oncogenic variants.

      Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691 2322:F691L

      Genes: 2322

      Variants: D835 D835Y F691 F691L

    3. FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Multiple FLT3 inhibitors are in various stages of clinical evaluation. However

      [Paragraph-level] PMCID: PMC8255005 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the resistance of FLT3 mutations, specifically F691L, to FLT3 inhibitors and highlights the efficacy of KX2-391 in overcoming this resistance, indicating a correlation with treatment response. Oncogenic: The FLT3 mutations, including D835 and F691, are described as contributing to tumor development and progression in acute myeloid leukemia (AML), which supports their classification as oncogenic variants.

      Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691 2322:F691L

      Genes: 2322

      Variants: D835 D835Y F691 F691L