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    1. Revealing very small FLT3 ITD mutated clones by ultra-deep sequencing analysis has important clinical implications in AML patients

      [Paper-level Aggregated] PMCID: PMC4741605

      Evidence Type(s): Oncogenic, Prognostic, Predictive

      Justification: Oncogenic: The presence of mutations D835Y, D839G, and D835H in FLT3 is associated with resistance to treatment and disease progression, indicating their role in oncogenesis. Prognostic: The mutations D835Y and D839G are linked to the patient's response to therapy and the likelihood of relapse, suggesting they can provide prognostic information regarding disease outcome. Predictive: The mutations D835Y, D839G, and D835H are associated with resistance to Sorafenib treatment, indicating their potential to predict treatment response.

      Gene→Variant (gene-first): FLT3(2322):D835H FLT3(2322):D839G FLT3(2322):D835Y

      Genes: FLT3(2322)

      Variants: D835H D839G D835Y

    2. Finally, patient UPN 2 was characterized by TKD D835Y mutation (43%) and a small ITD mutated clone (revealed only by UDS analysis, 0,4%) at diagnosis. After two months of conventional chemotherapy treatment (3+7 schedule

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 20

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of the patient to chemotherapy treatment and how the presence of the D835Y mutation correlates with the patient's relapse, indicating its potential role in therapeutic decisions. Oncogenic: The D835Y mutation is described as a mutation that contributes to the tumor's behavior, particularly in the context of the patient's relapse and the increase in the mutated clone's percentage.

      Gene→Variant (gene-first): 2322:D835Y

      Genes: 2322

      Variants: D835Y

    3. Patient UPN 5 showed resistance to conventional induction chemotherapy (Cytarabine and Idarubicine). UDS analysis revealed a progressive expansion of the ITD+ clone over time (from 3,78% at diagnosis to 12,3% two months

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 19

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the resistance of the D835Y variant to conventional induction chemotherapy and indicates that the treatment successfully inhibited the D835Y mutated clone, suggesting a correlation with treatment response. Oncogenic: The D835Y variant is mentioned in the context of tumor progression and its behavior in response to treatment, indicating its role in tumor development or progression.

      Gene→Variant (gene-first): 2322:D835Y

      Genes: 2322

      Variants: D835Y

    4. Patient UPN 4 received conventional induction chemotherapy and after an initial expansion of the FLT3 ITD+ clone, he achieved a complete morphological remission at the end of a "3+7" induction schedule. At molecular leve

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 18

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage states that the mutations D839G and D835H are able to confer resistance to Sorafenib treatment, indicating a correlation between these variants and treatment response. Oncogenic: The presence of the D839G and D835H mutations is associated with the evolution of the FLT3 ITD+ clone and suggests a role in tumor development or progression, particularly in the context of acute myeloid leukemia (AML).

      Gene→Variant (gene-first): 2322:D835H 2322:D839G

      Genes: 2322

      Variants: D835H D839G

    5. Patient UPN 3 received best supportive therapy (BST). The ITD+ clone progressively increased (from 1,34% at diagnosis to 29,4% after 14 months of follow-up), along with the appearance of a minor ITD+ clone (0,6%) and two

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 17

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the patient's response to the FLT3 inhibitor AC220-002, indicating that the presence of the D835Y and D839G variants may correlate with the patient's treatment response. Oncogenic: The D835Y and D839G variants are mentioned in the context of their abundance in the patient's sample, suggesting their potential role in tumor development or progression as part of the FLT3 mutation landscape.

      Gene→Variant (gene-first): 2322:D835Y 2322:D839G

      Genes: 2322

      Variants: D835Y D839G

    6. Finally, patient UPN 2 was characterized by TKD D835Y mutation (43%) and a small ITD mutated clone (revealed only by UDS analysis, 0,4%) at diagnosis. After two months of conventional chemotherapy treatment (3+7 schedule

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 20

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of the patient to chemotherapy treatment and how the presence of the D835Y mutation correlates with the patient's relapse, indicating its potential role in therapeutic decisions. Oncogenic: The D835Y mutation is described as a mutation that contributes to the tumor's behavior, particularly in the context of the patient's relapse and the increase in the mutated clone's percentage.

      Gene→Variant (gene-first): 2322:D835Y

      Genes: 2322

      Variants: D835Y

    7. Patient UPN 5 showed resistance to conventional induction chemotherapy (Cytarabine and Idarubicine). UDS analysis revealed a progressive expansion of the ITD+ clone over time (from 3,78% at diagnosis to 12,3% two months

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 19

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the resistance of the D835Y variant to conventional induction chemotherapy and indicates that the treatment successfully inhibited the D835Y mutated clone, suggesting a correlation with treatment response. Oncogenic: The D835Y variant is mentioned in the context of tumor progression and its behavior in response to treatment, indicating its role in tumor development or progression.

      Gene→Variant (gene-first): 2322:D835Y

      Genes: 2322

      Variants: D835Y

    8. Patient UPN 4 received conventional induction chemotherapy and after an initial expansion of the FLT3 ITD+ clone, he achieved a complete morphological remission at the end of a "3+7" induction schedule. At molecular leve

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 18

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage states that the mutations D839G and D835H are able to confer resistance to Sorafenib treatment, indicating a correlation between these variants and treatment response. Oncogenic: The presence of the D839G and D835H mutations is associated with the evolution of the FLT3 ITD+ clone and suggests a role in tumor development or progression, particularly in the context of acute myeloid leukemia (AML).

      Gene→Variant (gene-first): 2322:D835H 2322:D839G

      Genes: 2322

      Variants: D835H D839G

    9. Patient UPN 3 received best supportive therapy (BST). The ITD+ clone progressively increased (from 1,34% at diagnosis to 29,4% after 14 months of follow-up), along with the appearance of a minor ITD+ clone (0,6%) and two

      [Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 17

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the patient's response to the FLT3 inhibitor AC220-002, indicating that the presence of the D835Y and D839G variants may correlate with the patient's treatment response. Oncogenic: The D835Y and D839G variants are mentioned in the context of their abundance in the patient's sample, suggesting their potential role in tumor development or progression as part of the FLT3 mutation landscape.

      Gene→Variant (gene-first): 2322:D835Y 2322:D839G

      Genes: 2322

      Variants: D835Y D839G