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Gene | JAK2 |
Variant | V617F |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | JAK2 V617F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). V617F results in constitutive activation of Jak2 and downstream Stat5 and Erk, is transforming in cell culture, and leads to development of erythrocytosis in mouse models (PMID: 15858187, PMID: 15837627, PMID: 15793561, PMID: 28473624). |
Associated Drug Resistance | |
Category Variants Paths |
JAK2 mutant JAK2 act mut JAK2 V617F |
Transcript | NM_004972.4 |
gDNA | chr9:g.5073770G>T |
cDNA | c.1849G>T |
Protein | p.V617F |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001322194 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_004972.4 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322194.2 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322195 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_004972 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322195.2 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_004972.3 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322196 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322194.1 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322196.1 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322196.2 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
NM_001322195.1 | chr9:g.5073770G>T | c.1849G>T | p.V617F | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
JAK2 V617F | acute myeloid leukemia | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |