{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Marit MR"],"funding":["Canadian Institutes of Health Research"],"pagination":["e43437"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3420867"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(8)"],"pubmed_abstract":["<h4>Background</h4>The non-receptor tyrosine kinase JAK2 is implicated in a group of myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2-selective inhibitors are currently being evaluated in clinical trials. Data from drug-resistant chronic myeloid leukemia patients demonstrate that treatment with a small-molecule inhibitor generates resistance via mutation or amplification of BCR-ABL. We hypothesize that treatment with small molecule inhibitors of JAK2 will similarly generate inhibitor-resistant mutants in JAK2.<h4>Methodology</h4>In order to identify inhibitor-resistant JAK2 mutations a priori, we utilized TEL-JAK2 to conduct an in vitro random mutagenesis screen for JAK2 alleles resistant to JAK Inhibitor-I. Isolated mutat"],"journal":["PloS one"],"pubmed_title":["Random mutagenesis reveals residues of JAK2 critical in evading inhibition by a tyrosine kinase inhibitor."],"pmcid":["PMC3420867"],"funding_grant_id":["FRN-42428","FRN-79400"],"pubmed_authors":["Marit MR","Chohan M","Matthew N","Kuntz DA","Rose DR","Barber DL","Huang K"],"additional_accession":[]},"is_claimable":false,"name":"Random mutagenesis reveals residues of JAK2 critical in evading inhibition by a tyrosine kinase inhibitor.","description":"<h4>Background</h4>The non-receptor tyrosine kinase JAK2 is implicated in a group of myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2-selective inhibitors are currently being evaluated in clinical trials. Data from drug-resistant chronic myeloid leukemia patients demonstrate that treatment with a small-molecule inhibitor generates resistance via mutation or amplification of BCR-ABL. We hypothesize that treatment with small molecule inhibitors of JAK2 will similarly generate inhibitor-resistant mutants in JAK2.<h4>Methodology</h4>In order to identify inhibitor-resistant JAK2 mutations a priori, we utilized TEL-JAK2 to conduct an in vitro random mutagenesis screen for JAK2 alleles resistant to JAK Inhibitor-I. Isolated mutat","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012","modification":"2026-04-18T09:10:59.766Z","creation":"2026-04-07T14:35:34.546Z"},"accession":"S-EPMC3420867","cross_references":{"pubmed":["22916261"],"doi":["10.1371/journal.pone.0043437"]}}