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Ref Type Journal Article
PMID (31976485)
Authors Govaerts I, Jacobs K, Vandepoel R, Cools J
Title JAK/STAT Pathway Mutations in T-ALL, Including the STAT5B N642H Mutation, are Sensitive to JAK1/JAK3 Inhibitors.
Journal HemaSphere
Vol 3
Issue 6
Date 2019 Dec
URL
Abstract Text

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Upadacitinib Rinvoq JAK1 Inhibitor 9 JAK3 Inhibitor 5 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).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
JAK3 L875H missense gain of function - predicted JAK3 L875H lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). L875H results in transforming activity in cultured cells (PMID: 29187379) and demonstrates resistance to some JAK inhibitors in culture (PMID: 31976485), and therefore, is predicted to lead to a gain of Jak3 protein function. Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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
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 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 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 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 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 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 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 L857H 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 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 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 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 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