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Molecular Profile	Treatment Approach
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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
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Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Upadacitinib	Upadacitinib	3	0

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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Upadacitinib	Rinvoq	ABT 494\|ABT-494	JAK1 Inhibitor 9 JAK3 Inhibitor 6	Rinvoq (upadacitinib) is an inhibitor of JAK1 and JAK3, which may lead to decreased cell proliferation (PMID: 31976485). Rinvoq (upadacitinib) is FDA approved for rheumatoid arthritis (FDA.gov).

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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
JAK3	L875H	missense	gain of function	JAK3 L875H lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L875H results in transforming activity (PMID: 29187379), receptor-independent Jak3 activation (PMID: 26446793), and demonstrates resistance to some JAK inhibitors in culture (PMID: 31976485).	Y

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
JAK1 A634D	hematologic cancer	sensitive	Tofacitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK1 A634D were sensitive to treatment with Xeljanz (tofacitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK1 A634D	hematologic cancer	sensitive	Upadacitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK1 A634D were sensitive to treatment with Rinvoq (upadacitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK1 A634D	hematologic cancer	sensitive	Ruxolitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK1 A634D were sensitive to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK1 A634D	hematologic cancer	sensitive	Decernotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK1 A634D were sensitive to treatment with Decernotinib (VX-509) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK1 A634D	hematologic cancer	sensitive	Baricitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK1 A634D were sensitive to treatment with Baricitinib (LY3009104) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK1 A634D	hematologic cancer	sensitive	ASP015K	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK1 A634D were sensitive to treatment with ASP015K (peficitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L857Q	hematologic cancer	sensitive	ASP015K	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L857Q were sensitive to treatment with ASP015K (peficitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L857Q	hematologic cancer	sensitive	Ruxolitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L857Q were sensitive to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L857Q	hematologic cancer	sensitive	Tofacitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L857Q were sensitive to treatment with Xeljanz (tofacitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L857Q	hematologic cancer	sensitive	Decernotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L857Q were sensitive to treatment with Decernotinib (VX-509) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L857Q	hematologic cancer	sensitive	Upadacitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L857Q were sensitive to treatment with Rinvoq (upadacitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L857Q	hematologic cancer	sensitive	Baricitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L857Q were sensitive to treatment with Baricitinib (LY3009104) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 L875H	hematologic cancer	predicted - sensitive	ASP015K	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L875H demonstrated some sensitivity to treatment with ASP015K (peficitinib) in culture, but were not as sensitive as cells expressing other JAK3 activating mutations (PMID: 31976485).	31976485
JAK3 L875H	hematologic cancer	predicted - sensitive	Tofacitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L875H demonstrated some sensitivity to treatment with Xeljanz (tofacitinib) in culture, but were not as sensitive as cells expressing other JAK3 activating mutations (PMID: 31976485).	31976485
JAK3 L875H	hematologic cancer	resistant	Baricitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L875H demonstrated resistance to treatment with Baricitinib (LY3009104) in culture (PMID: 31976485).	31976485
JAK3 L875H	hematologic cancer	predicted - sensitive	Ruxolitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L875H demonstrated some sensitivity to treatment with Jakafi (ruxolitinib) in culture, but were not as sensitive as cells expressing other JAK3 activating mutations (PMID: 31976485).	31976485
JAK3 L875H	hematologic cancer	predicted - sensitive	Decernotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L875H demonstrated some sensitivity to treatment with Decernotinib (VX-509) in culture, but were not as sensitive as cells expressing other JAK3 activating mutations (PMID: 31976485).	31976485
JAK3 L875H	hematologic cancer	resistant	Upadacitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 L875H demonstrated resistance to treatment with Rinvoq (upadacitinib) in culture (PMID: 31976485).	31976485
JAK3 M511I	hematologic cancer	sensitive	Decernotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with Decernotinib (VX-509) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 M511I	hematologic cancer	sensitive	Baricitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with Baricitinib (LY3009104) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 M511I	hematologic cancer	sensitive	Ruxolitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485
JAK3 M511I	hematologic cancer	sensitive	ASP015K	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with ASP015K (peficitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485).	31976485

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