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Profile Name FLT3 exon 14 ins JAK3 V722I
Gene Variant Detail

FLT3 exon 14 ins (gain of function - predicted)

JAK3 V722I (gain of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Midostaurin + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited downstream signaling and cell growth in transformed hematologic cells expressing aa FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Gilteritinib + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer decreased response Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I acute myeloid leukemia predicted - resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Nexavar (sorafenib) was found to have acquired a JAK3 V722I mutation with a variant allele frequency of 49% upon relapse (PMID: 33149267). 33149267