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Profile Name JAK2 V617F
Gene Variant Detail

JAK2 V617F (gain of function)

Relevant Treatment Approaches JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK2 V617F acute myeloid leukemia sensitive JAK2 Inhibitor Go6976 Preclinical Actionable In a preclinical study, Go 6976 inhibited proliferation of cultured acute myeloid leukemia cells expressing the JAK2 V617F mutation (PMID: 16956345). 16956345
JAK2 V617F acute myeloid leukemia sensitive A-1155463 Preclinical Actionable In a preclinical study, acute myeloid leukemia cells harboring JAK2 V617F demonstrated sensitivity to A-1155463 in culture (PMID: 25787766). 25787766
JAK2 V617F bone marrow cancer decreased response SGI-1776 Preclinical Actionable In a preclinical study, myeloproliferative cancer cell lines harboring JAK2 V617F demonstrated reduced sensitivity to SGI-1776 induced growth inhibition in culture (PMID: 26472029). 26472029
JAK2 V617F bone marrow cancer decreased response AZD1208 Preclinical Actionable In a preclinical study, myeloproliferative cancer cell lines harboring JAK2 V617F demonstrated reduced sensitivity to AZD1208 induced growth inhibition in culture (PMID: 26472029). 26472029
JAK2 V617F bone marrow cancer sensitive JAK2 Inhibitor - ATP competitive Ruxolitinib + SGI-1776 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) worked synergistically with SGI-1776 to inhibit proliferation of myeloproliferative cancer cell lines harboring JAK2 V617F in culture (PMID: 26472029). 26472029
JAK2 V617F bone marrow cancer sensitive JAK2 Inhibitor - ATP competitive AZD1208 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) worked synergistically with AZD1208 to inhibit proliferation of myeloproliferative cancer cell lines harboring JAK2 V617F in culture (PMID: 26472029). 26472029
JAK2 V617F acute myeloid leukemia sensitive JAK2 Inhibitor - ATP competitive Ruxolitinib + Tenalisib Preclinical Actionable In a preclinical study, Tenalisib (RP6530) worked synergistically with Jakafi (ruxolitinib) to inhibit proliferation of Jakafi (ruxolitinib)-resistant erythroleukemia cell lines carrying JAK2 V617F mutation ( Cancer Res August 1, 2015 75; 2704 ). detail...
JAK2 V617F Advanced Solid Tumor sensitive JAK2 Inhibitor - ATP competitive Ruxolitinib + ZSTK474 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and ZSTK474 synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F Advanced Solid Tumor sensitive JAK2 Inhibitor - ATP competitive Pictilisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Pictilisib (GDC-0941) synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F Advanced Solid Tumor sensitive JAK2 Inhibitor - ATP competitive Dactolisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and BEZ235 synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F Advanced Solid Tumor sensitive JAK2 Inhibitor - ATP competitive Ruxolitinib + TGX-221 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and TGX-221 synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F bone marrow cancer sensitive JAK2 Inhibitor CHZ868 Preclinical Actionable In a preclinical study, CHZ868 inhibited proliferation of myeloproliferative neoplasm cells harboring JAK2 V617F , including cells with decreased response to Type I JAK inhibitors following chronic exposure, and decreased mutant allele burden in a mouse polycythemia vera model expressing JAK2 V617F (PMID: 26175413). 26175413
JAK2 V617F myeloid leukemia resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed mouse myeloid cells over expressing JAK2 V617F were resistant to Gleevec (imatinib) in culture (PMID: 21224473). 21224473
JAK2 V617F hematologic cancer sensitive SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 inhibited proliferation of a hematopoietic cancer cell line harboring JAK2 V617F in culture (PMID: 27362227). 27362227
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor - ATP competitive Ilginatinib Preclinical Actionable In a preclinical study, cells expressing JAK2 V617F were sensitive to treatment with Ilginatinib (NS-018), demonstrating cell growth inhibition and increased apoptotic activity in culture and improved survival in transgenic mouse models (PMID: 22829185). 22829185
JAK2 V617F essential thrombocythemia sensitive JAK2 Inhibitor - ATP competitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited proliferation and induced apoptosis in an essential thrombocythemia cell line harboring JAK2 V617F in culture (PMID: 22015772). 22015772
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor - ATP competitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited proliferation of transformed cells expressing JAK2 V617F in culture (PMID: 22015772). 22015772
JAK2 V617F myeloproliferative neoplasm sensitive JAK2 Inhibitor - ATP competitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited colony growth in myeloproliferative neoplasm patient-derived hematopoetic progenitor cells harboring JAK2 V617F in culture (PMID: 22015772). 22015772
JAK2 V617F myeloproliferative neoplasm predicted - sensitive JAK2 Inhibitor - ATP competitive Gandotinib Phase I Actionable In a Phase I trial, treatment with Gandotinib (LY2784544) demonstrated safety in myeloproliferative neoplasm patients harboring JAK2 V617F and resulted in clinical improvement as best response in 29% (9/31) patients with myelofibrosis (PMID: 28934680). 28934680
JAK2 V617F myelofibrosis not applicable N/A Guideline Prognostic JAK2 V617F is associated with intermediate prognosis and higher risk of thrombosis when compared to the presence of CALR mutations in patients with primary myelofibrosis (NCCN.org). detail...
JAK2 V617F myeloproliferative neoplasm sensitive Ropeginterferon Preclinical - Cell culture Actionable In a preclinical study, Ropeginterferon treatment resulted in dose-dependent inhibition of cell proliferation in myeloproliferative neoplasm cell lines harboring JAK2 V617F in culture (PMID: 30287855). 30287855
JAK2 V617F acute megakaryocytic leukemia sensitive Ropeginterferon Preclinical - Cell culture Actionable In a preclinical study, a megakaryoblastic leukemia cell line expressing JAK2 V617F demonstrated inhibition of cell proliferation in culture when treated with Ropeginterferon (PMID: 30287855). 30287855
JAK2 V617F polycythemia vera sensitive Ropeginterferon Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived erythroid progenitors harboring JAK2 V617F demonstrated sensitivity to Ropeginterferon in culture (PMID: 30287855). 30287855
JAK2 V617F polycythemia vera sensitive Ropeginterferon Clinical Study - Cohort Actionable In a clinical study using data from a Phase III trial, polycythemia vera patients demonstrated significant reduction in the median JAK2 V617F mutational burden at 12 months following treatment with Ropeginterferon compared to Droxia (hydroxyurea) (13.8% vs. 33.2%; p<0.02) (PMID: 30287855; NCT01949805). 30287855
JAK2 V617F polycythemia vera predicted - sensitive INCB053914 Preclinical - Patient cell culture Actionable In a preclinical study, INCB053914 inhibited erythroid colony formation in cells derived from patients with myeloproliferative neoplasms, including polycythemia vera, harboring JAK2 V617F in culture (PMID: 29927999). 29927999
JAK2 V617F essential thrombocythemia predicted - sensitive INCB053914 Preclinical - Patient cell culture Actionable In a preclinical study, INCB053914 inhibited erythroid colony formation in cells derived from patient with myeloproliferative neoplasms (MPNs), including essential thrombocythemia, harboring JAK2 V617F in culture (PMID: 29927999). 29927999
JAK2 V617F myelofibrosis predicted - sensitive INCB053914 Preclinical - Patient cell culture Actionable In a preclinical study, INCB053914 inhibited erythroid colony formation in cells derived from patients with myeloproliferative neoplasms (MPNs), including primary myelofibrosis, harboring JAK2 V617F in culture (PMID: 29927999). 29927999
JAK2 V617F polycythemia vera not applicable N/A Guideline Diagnostic JAK2 V617F aids in the diagnosis of polycythemia vera (NCCN.org). detail...
JAK2 V617F hematologic cancer predicted - sensitive C220 Preclinical - Cell culture Actionable In a preclinical study, C220 treatment inhibited proliferation of transformed cells expressing JAK2 V617F in culture (PMID: 32669286). 32669286
JAK2 V617F polycythemia vera predicted - sensitive C220 Preclinical Actionable In a preclinical study, C220 treatment in a transgenic mouse model of polycythemia vera expressing JAK2 V617F resulted in decreased white blood cell counts, reduced spleen size with decreased extramedullary hematopoeisis, and decreased myeloproliferation, and altered the proportion of erythroid progenitors and erythroblasts (PMID: 32669286). 32669286
JAK2 V617F polycythemia vera predicted - sensitive JAK2 Inhibitor - ATP competitive C220 + Ruxolitinib Preclinical Actionable In a preclinical study, combination of C220 and Jakafi (ruxolitinib) treatment in a transgenic mouse model of polycythemia vera expressing JAK2 V617F resulted in reduced white blood cell count, decreased spleen and liver size, reduced bone marrow hypercellularity, reduced erythroid, megakaryocyte and myeloid progenitors, and inhibition of inflammatory cytokines to a greater degree than single agent alone. (PMID: 32669286). 32669286
JAK2 V617F myeloproliferative neoplasm predicted - sensitive C220 Preclinical - Cell line xenograft Actionable In a preclinical study, C220 treatment inhibited cell proliferation of myeloproliferative neoplasm cell lines, including a Jakafi (ruxolitinib)-persistent cell line, expressing JAK2 V617F in culture, and inhibited tumor growth, with a 71% tumor reduction, in a cell line xenograft model (PMID: 32669286). 32669286
JAK2 V617F myeloproliferative neoplasm predicted - sensitive JAK2 Inhibitor - ATP competitive C220 + Ruxolitinib Preclinical - Cell line xenograft Actionable In a preclinical study, combination of C220 and Jakafi (ruxolitinib) treatment led to additive effects, resulting in inhibition of proliferation of myeloproliferative neoplasm cell lines expressing JAK2 V617F in culture, and inhibited tumor growth, with a 73% tumor reduction, in a cell line xenograft model (PMID: 32669286). 32669286
JAK2 V617F myelofibrosis predicted - sensitive C220 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived primary myelofibrosis cells harboring JAK2 V617F and positive for CD34 were sensitive to C220 treatment in culture (PMID: 32669286). 32669286
JAK2 V617F leukemia predicted - sensitive JAK2 Inhibitor - ATP competitive LGH447 + Ribociclib + Ruxolitinib Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment with Jakafi (ruxolitinib), LGH447, and Kisqali (ribociclib) led to complete tumor regression in a cell line xenograft model of leukemia harboring JAK2 V617F (PMID: 33782031). 33782031
JAK2 V617F myeloproliferative neoplasm sensitive JAK2 Inhibitor - ATP competitive LGH447 + Ribociclib + Ruxolitinib Preclinical Actionable In a preclinical study, combination treatment with Jakafi (ruxolitinib), LGH447, and Kisqali (ribociclib) led to decreased white blood cell and platelet counts, decreased spleen size compared to Jakafi (ruxolitinib) treatment alone, and normocellular bone marrow with appropriate maturation a mouse model of myeloproliferative neoplasm harboring JAK2 V617F (PMID: 33782031). 33782031
JAK2 V617F acute megakaryocytic leukemia sensitive JAK2 Inhibitor - ATP competitive AZ960 Preclinical - Cell culture Actionable In a preclinical study, AZ960 treatment induced apoptosis, decreased Stat3/5 phosphorylation and downstream signaling, and inhibited proliferation of a megakaryoblastic leukemia cell line harboring JAK2 V617F in culture (PMID: 18775810). 18775810
JAK2 V617F hematologic cancer predicted - sensitive IMG-7289 Preclinical - Cell culture Actionable In a preclinical study, IMG-7289 treatment led to increased apoptosis induction in transformed cells expressing JAK2 V617F compared to cells expressing wild-type Jak2 in culture (PMID: 31723778). 31723778
JAK2 V617F myeloproliferative neoplasm sensitive IMG-7289 Preclinical Actionable In a preclinical study, IMG-7289 treatment led to decreased JAK2 V617F allele burden in peripheral blood cells and splenic cells, decreased spleen size, and improved survival in a transgenic mouse model of myeloproliferative neoplasm expressing JAK2 V617F (PMID: 31723778). 31723778
JAK2 V617F myeloproliferative neoplasm predicted - sensitive JAK2 Inhibitor - ATP competitive IMG-7289 + Ruxolitinib Preclinical Actionable In a preclinical study, combination treatment with Jakafi (ruxolitinib) and IMG-7289 demonstrated a synergistic effect, and led to decreased leukocyte and platelet counts, decreased spleen size, and decreased bone marrow stem and progenitor cell expansion in a transgenic mouse model expressing JAK2 V617F (PMID: 31723778). 31723778
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor - ATP competitive Momelotinib Preclinical - Cell culture Actionable In a preclinical study, Momelotinib (CYT387) inhibited proliferation of transformed cells expressing JAK2 V617F in culture (PMID: 34768286). 34768286
JAK2 V617F polycythemia vera sensitive JAK2 Inhibitor - ATP competitive Binimetinib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Mektovi (binimetinib) combination treatment resulted in increased inhibition of Erk phosphorylation and signaling, decreased splenomegaly, hematocrit, and reticulocytes, and decreased bone marrow fibrosis in a mouse model of polycythemia vera harboring JAK2 V617F compared to either drug alone (PMID: 30730307). 30730307
JAK2 V617F polycythemia vera sensitive JAK2 Inhibitor Binimetinib + CHZ868 Preclinical Actionable In a preclinical study, CHZ868 and Mektovi (binimetinib) combination treatment decreased splenomegaly, reticulocytes, hematocrit, and allele burden, and reduced expansion of progenitor cells, an effect not observed with treatment of either agent alone, in a mouse model of polycythemia vera harboring JAK2 V617F (PMID: 30730307). 30730307
JAK2 V617F myelofibrosis sensitive JAK2 Inhibitor - ATP competitive Binimetinib + Ruxolitinib Preclinical - Patient cell culture Actionable In a preclinical study, Jakafi (ruxolitinib) and Mektovi (binimetinib) combination treatment resulted in enhanced inhibition of colony growth in bone marrow and peripheral blood mononuclear cells (PBMCs) derived from myelofibrosis patients harboring JAK2 V617F in culture compared to Jakafi (ruxolitinib) alone (PMID: 30730307). 30730307
JAK2 V617F polycythemia vera sensitive Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited colony formation and Stat5 phosphorylation in polycythemia vera cultured cells derived from an EML4-ALK-positive non-small cell lung cancer patient who was diagnosed with polycythemia vera and found to harbor JAK2 V617F (PMID: 36537918). 36537918
JAK2 V617F hematologic cancer sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited cell proliferation and phosphorylation of Stat3, Jak2, and Ron in hematopoietic cell lines harboring JAK2 V617F in culture (PMID: 36537918). 36537918
JAK2 V617F myeloproliferative neoplasm sensitive Crizotinib Preclinical Actionable In a preclinical study, Xalkori (crizotinib) treatment resulted in reduced spleen weights in a myeloproliferative neoplasm knock-in mouse model expressing JAK2 V617F (PMID: 36537918). 36537918
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor Flonoltinib maleate Preclinical Actionable In a preclinical study, Flonoltinib maleate inhibited Jak2 downstream signaling and proliferation and induced apoptosis in a cell line expressing JAK2 V617F in culture and increased survival in a mouse model (PMID: 35256594). 35256594
JAK2 V617F myelofibrosis sensitive JAK2 Inhibitor Flonoltinib maleate Preclinical Actionable In a preclinical study, Flonoltinib maleate decreased splenomegaly and improved survival in a mouse model of myelofibrosis harboring JAK2 V617F (PMID: 35256594). 35256594
JAK2 V617F myeloproliferative neoplasm sensitive JAK2 Inhibitor Flonoltinib maleate Preclinical - Cell culture Actionable In a preclinical study, Flonoltinib maleate inhibited Jak/Stat signaling and colony formation in myeloproliferative neoplasm patient-derived cells harboring JAK2 V617F in culture (PMID: 35256594). 35256594
JAK2 V617F acute myeloid leukemia sensitive JAK2 Inhibitor Flonoltinib maleate Preclinical - Cell culture Actionable In a preclinical study, Flonoltinib maleate inhibited Jak/Stat signaling and cell cycle progression and induced apoptosis in an acute myeloid leukemia cell line harboring JAK2 V617F in culture (PMID: 35256594). 35256594
JAK2 V617F hematologic cancer predicted - sensitive JAK2 Inhibitor INCB160058 Preclinical Actionable In a preclinical study, INCB160058 inhibited tumor growth in a mouse model of hematologic cancer expressing JAK2 V617F (Blood (2023) 142 (Supplement 1): 860). detail...
JAK2 V617F myelofibrosis predicted - sensitive JAK2 Inhibitor INCB160058 Preclinical - Patient cell culture Actionable In a preclinical study, INCB160058 decreased Stat5 phosphorylation, abnormal megakaryopoiesis, and colony formation in human hematopoietic stem cells derived from patients with myelofibrosis harboring JAK2 V617F in culture (Blood (2023) 142 (Supplement 1): 860). detail...
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor - ATP competitive Fedratinib Preclinical - Cell culture Actionable In a preclinical study, Inrebic (fedratinib) inhibited Stat5 signaling and proliferation in a cell line expressing JAK2 V617F in culture (PMID: 39091915). 39091915
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor - ATP competitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, Jakafi (ruxolitinib) inhibited Stat5 signaling and proliferation in a cell line expressing JAK2 V617F in culture (PMID: 39091915). 39091915
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor - ATP competitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, Lestaurtinib (CEP-701) inhibited Stat5 signaling and proliferation in a cell line expressing JAK2 V617F in culture (PMID: 39091915). 39091915
JAK2 V617F hematologic cancer sensitive JAK2 Inhibitor CHZ868 Preclinical - Cell culture Actionable In a preclinical study, CHZ868 inhibited Stat5 signaling and proliferation in a cell line expressing JAK2 V617F in culture (PMID: 39091915). 39091915
JAK2 V617F hematologic cancer sensitive Tanespimycin Preclinical - Cell culture Actionable In a preclinical study, Tanespimycin (17-AAG) inhibited Stat5 signaling and proliferation in a cell line expressing JAK2 V617F in culture (PMID: 39091915). 39091915
JAK2 V617F hematologic cancer sensitive Geldanamycin Preclinical - Cell culture Actionable In a preclinical study, Geldanamycin inhibited Stat5 signaling and proliferation in a cell line expressing JAK2 V617F in culture (PMID: 39091915). 39091915