Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
[Paper-level Aggregated] PMCID: PMC5613053
Evidence Type(s): Functional
Summary: Mutation: F691 | Summary: The F691 position is noted for its hydrophobic interaction with gilteritinib, indicating a functional alteration in the molecular interaction with the drug.
Gene→Variant (gene-first): FLT3(2322):F691
Genes: FLT3(2322)
Variants: F691
Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
[Paper-level Aggregated] PMCID: PMC5613053
Evidence Type(s): Prognostic
Summary: Mutation: D835Y | Summary: The D835Y mutation in FLT3 is linked to poor overall survival in patients with AML, indicating its prognostic significance independent of therapy.
Evidence Type: Prognostic Mutation: F691 | Summary: The F691 mutation in FLT3 is associated with poor overall survival in AML, highlighting its prognostic implications.
Gene→Variant (gene-first): FLT3(2322):D835Y FLT3(2322):F691
Genes: FLT3(2322)
Variants: D835Y F691
Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
[Paper-level Aggregated] PMCID: PMC5613053
Evidence Type(s): Predictive
Summary: Mutation: D835Y | Summary: The D835Y mutation in FLT3 is associated with response to the FLT3/AXL inhibitor gilteritinib, indicating its predictive value for treatment efficacy in AML. It is also associated with resistance to FLT3 inhibitors, suggesting a correlation with treatment response and sensitivity to gilteritinib.
Evidence Type: Predictive Mutation: F691 | Summary: The F691 mutation in FLT3 is associated with response to gilteritinib, indicating its predictive role in treatment outcomes for AML. It is also implicated in resistance to FLT3 inhibitors, suggesting it affects the response to gilteritinib treatment. The F691 L/I mutation is similarly associated with response to gilteritinib, while the F691 L and F691I mutations are noted for their role in resistance to FLT3 inhibitors.
Gene→Variant (gene-first): FLT3(2322):D835Y FLT3(2322):F691
Genes: FLT3(2322)
Variants: D835Y F691
The finding that gilteritinib inhibited FLT3-D835Y and FLT3-ITD-D835Y, both of which harbor mutations in the activation loop essential for binding type 2 inhibitors, suggests that gilteritinib is a type 1 FLT3 inhibitor.
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 12
Evidence Type(s): Predictive, Functional
Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The mutation D835Y is associated with the response to gilteritinib, a type 1 FLT3 inhibitor, indicating its predictive value for therapy. Evidence Type: Predictive | Mutation: D835 | Summary: The mutation D835 is implicated in the response to gilteritinib, suggesting its role in predicting treatment outcomes. Evidence Type: Functional | Mutation: F691 | Summary: The F691 position is noted for its hydrophobic interaction with gilteritinib, indicating a functional alteration in the molecular interaction with the drug.
Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691
Genes: 2322
Variants: D835 D835Y F691
Since mutations within the TKD of FLT3 (eg, FLT3-D835Y or FLT3-F691) often confer resistance to FLT3 inhibitors that were previously effective against FLT3-ITD, the effect of gilteritinib on these resistance mutations wa
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 10
Evidence Type(s): Predictive
Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation is associated with resistance to FLT3 inhibitors, indicating a correlation with treatment response and sensitivity to gilteritinib. Evidence Type: Predictive | Mutation: F691 | Summary: The F691 mutation is implicated in resistance to FLT3 inhibitors, suggesting it affects the response to gilteritinib treatment. Evidence Type: Predictive | Mutation: F691 L | Summary: The F691 L mutation is associated with resistance to FLT3 inhibitors, indicating a correlation with treatment response and sensitivity to gilteritinib. Evidence Type: Predictive | Mutation: F691I | Summary: The F691I mutation is implicated in resistance to FLT3 inhibitors, suggesting it affects the response to gilteritinib treatment.
Gene→Variant (gene-first): 2322:D835Y 2322:F691 2322:F691 L 2322:F691I
Genes: 2322
Variants: D835Y F691 F691 L F691I
Inhibitory activity of gilteritinib against FLT3 containing ITD +- D835Y or F691 L/I mutations
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 9
Evidence Type(s): Predictive
Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation is associated with the response to gilteritinib, indicating its predictive value for therapy sensitivity. Evidence Type: Predictive | Mutation: F691 L/I | Summary: The F691 L/I mutation is associated with the response to gilteritinib, indicating its predictive value for therapy sensitivity.
Gene→Variant (gene-first): 2322:D835Y 2322:F691 L/I
Genes: 2322
Variants: D835Y F691 L/I
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in A
[Paragraph-level] PMCID: PMC5613053 Section: ABSTRACT PassageIndex: 2
Evidence Type(s): Predictive, Prognostic
Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation in FLT3 is associated with response to the FLT3/AXL inhibitor gilteritinib, indicating its predictive value for treatment efficacy in AML. Evidence Type: Predictive | Mutation: F691 | Summary: The F691 mutation in FLT3 is also associated with response to gilteritinib, suggesting its predictive role in treatment outcomes for AML. Evidence Type: Prognostic | Mutation: D835Y | Summary: The D835Y mutation in FLT3 is linked to poor overall survival in patients with AML, indicating its prognostic significance independent of therapy. Evidence Type: Prognostic | Mutation: F691 | Summary: The F691 mutation in FLT3 is associated with poor overall survival in AML, highlighting its prognostic implications.
Gene→Variant (gene-first): 2322:D835Y 2322:F691
Genes: 2322
Variants: D835Y F691
Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
[Paper-level Aggregated] PMCID: PMC5613053
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The text indicates that mutations in FLT3, including D835Y and F691, are associated with poor overall survival in AML, suggesting their role in cancer progression. Predictive: The evidence shows that gilteritinib effectively inhibits cell growth in models expressing FLT3 mutations (D835Y, F691), indicating its potential as a predictive biomarker for treatment response in FLT3 mutation-positive AML. Functional: The study demonstrates that gilteritinib inhibits the activity of mutated FLT3, affecting downstream signaling pathways and leading to tumor regression, which reflects the functional impact of these mutations on drug efficacy.
Gene→Variant (gene-first): FLT3(2322):D835 FLT3(2322):D835Y FLT3(2322):F691 FLT3(2322):F691 L/I FLT3(2322):F691 L FLT3(2322):F691I
Genes: FLT3(2322)
Variants: D835 D835Y F691 F691 L/I F691 L F691I
The finding that gilteritinib inhibited FLT3-D835Y and FLT3-ITD-D835Y, both of which harbor mutations in the activation loop essential for binding type 2 inhibitors, suggests that gilteritinib is a type 1 FLT3 inhibitor.
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 12
Evidence Type(s): Predictive, Functional
Justification: Predictive: The passage discusses how gilteritinib inhibits FLT3-D835Y and FLT3-ITD-D835Y, indicating a correlation between the variant and response to the therapy, which is a predictive context. Functional: The passage describes how gilteritinib interacts with FLT3 at the F691 position and discusses the structural implications of the D835Y mutation, indicating an alteration in molecular function related to the binding of the inhibitor.
Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691
Genes: 2322
Variants: D835 D835Y F691
Since mutations within the TKD of FLT3 (eg, FLT3-D835Y or FLT3-F691) often confer resistance to FLT3 inhibitors that were previously effective against FLT3-ITD, the effect of gilteritinib on these resistance mutations wa
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 10
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses how mutations such as FLT3-D835Y and FLT3-F691 confer resistance to FLT3 inhibitors, indicating a correlation with treatment response and sensitivity to specific therapies like gilteritinib and quizartinib. Oncogenic: The variants FLT3-D835Y and FLT3-F691 are implicated in tumor development and progression, as evidenced by their expression in Ba/F3 cells and the observed antitumor efficacy of gilteritinib in xenograft models.
Gene→Variant (gene-first): 2322:D835Y 2322:F691 2322:F691 L 2322:F691I
Genes: 2322
Variants: D835Y F691 F691 L F691I
Inhibitory activity of gilteritinib against FLT3 containing ITD +- D835Y or F691 L/I mutations
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 9
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses the inhibitory activity of gilteritinib against FLT3 containing specific mutations, indicating a correlation with response to therapy. Oncogenic: The mention of D835Y and F691 L/I mutations in the context of FLT3 suggests that these somatic variants contribute to tumor development or progression.
Gene→Variant (gene-first): 2322:D835Y 2322:F691 L/I
Genes: 2322
Variants: D835Y F691 L/I
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in A
[Paragraph-level] PMCID: PMC5613053 Section: ABSTRACT PassageIndex: 2
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses the ability of gilteritinib to block mutated FLT3, including the D835Y and F691 mutations, and its correlation with improved survival in models of FLT3-driven AML, indicating a response to therapy. Oncogenic: The D835Y and F691 mutations in FLT3 are implicated in the pathogenesis of acute myeloid leukemia (AML), suggesting that these somatic variants contribute to tumor development or progression.
Gene→Variant (gene-first): 2322:D835Y 2322:F691
Genes: 2322
Variants: D835Y F691
The finding that gilteritinib inhibited FLT3-D835Y and FLT3-ITD-D835Y, both of which harbor mutations in the activation loop essential for binding type 2 inhibitors, suggests that gilteritinib is a type 1 FLT3 inhibitor.
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 12
Evidence Type(s): Predictive, Functional
Justification: Predictive: The passage discusses how gilteritinib inhibits FLT3-D835Y and FLT3-ITD-D835Y, indicating a correlation between the variant and response to the therapy, which is a predictive context. Functional: The passage describes how gilteritinib interacts with FLT3 at the F691 position and discusses the structural implications of the D835Y mutation, indicating an alteration in molecular function related to the binding of the inhibitor.
Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691
Genes: 2322
Variants: D835 D835Y F691
Since mutations within the TKD of FLT3 (eg, FLT3-D835Y or FLT3-F691) often confer resistance to FLT3 inhibitors that were previously effective against FLT3-ITD, the effect of gilteritinib on these resistance mutations wa
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 10
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses how mutations such as FLT3-D835Y and FLT3-F691 confer resistance to FLT3 inhibitors, indicating a correlation with treatment response and sensitivity to specific therapies like gilteritinib and quizartinib. Oncogenic: The variants FLT3-D835Y and FLT3-F691 are implicated in tumor development and progression, as evidenced by their expression in Ba/F3 cells and the observed antitumor efficacy of gilteritinib in xenograft models.
Gene→Variant (gene-first): 2322:D835Y 2322:F691 2322:F691 L 2322:F691I
Genes: 2322
Variants: D835Y F691 F691 L F691I
Inhibitory activity of gilteritinib against FLT3 containing ITD +- D835Y or F691 L/I mutations
[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 9
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses the inhibitory activity of gilteritinib against FLT3 containing specific mutations, indicating a correlation with response to therapy. Oncogenic: The mention of D835Y and F691 L/I mutations in the context of FLT3 suggests that these somatic variants contribute to tumor development or progression.
Gene→Variant (gene-first): 2322:D835Y 2322:F691 L/I
Genes: 2322
Variants: D835Y F691 L/I
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in A
[Paragraph-level] PMCID: PMC5613053 Section: ABSTRACT PassageIndex: 2
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses the ability of gilteritinib to block mutated FLT3, including the D835Y and F691 mutations, and its correlation with improved survival in models of FLT3-driven AML, indicating a response to therapy. Oncogenic: The D835Y and F691 mutations in FLT3 are implicated in the pathogenesis of acute myeloid leukemia (AML), suggesting that these somatic variants contribute to tumor development or progression.
Gene→Variant (gene-first): 2322:D835Y 2322:F691
Genes: 2322
Variants: D835Y F691