{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Oravecz-Wilson KI"],"funding":["Howard Hughes Medical Institute","NCI NIH HHS"],"pagination":["137-48"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2763369"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(2)"],"pubmed_abstract":["Despite remarkable responses to the tyrosine kinase inhibitor imatinib, CML patients are rarely cured by this therapy perhaps due to imatinib refractoriness of leukemia-initiating cells (LICs). Evidence for this is limited because of poor engraftment of human CML-LICs in NOD-SCID mice and nonphysiologic expression of oncogenes in retroviral transduction mouse models. To address these challenges, we generated mice bearing conditional knockin alleles of two human oncogenes: HIP1/PDGFbetaR (H/P) and AML1-ETO (A/E). Unlike retroviral transduction, physiologic expression of H/P or A/E individually failed to induce disease, but coexpression of both H/P and A/E led to rapid onset of a fully penetrant, myeloproliferative disorder, indicating cooperativity between these two alleles. Although imatin"],"journal":["Cancer cell"],"pubmed_title":["Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder."],"pmcid":["PMC2763369"],"funding_grant_id":["R01 CA098730-01","T32 CA009676","R01 CA082363-05","R01 CA082363-04","R01 CA082363","CA009676","R01 CA082363-03","R01 CA098730-04S1","R01 CA082363-02","R01 CA082363-01A1","R01 CA82363-03","R01 CA098730-05A1","R01 CA098730"],"pubmed_authors":["Sitwala K","Ross TS","Crawford BD","Ames HM","Gauvin AM","Morrison SJ","Philips ST","Yilmaz OH","Downing JR","Lucas PC","Li L","Oravecz-Wilson KI"],"additional_accession":[]},"is_claimable":false,"name":"Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder.","description":"Despite remarkable responses to the tyrosine kinase inhibitor imatinib, CML patients are rarely cured by this therapy perhaps due to imatinib refractoriness of leukemia-initiating cells (LICs). Evidence for this is limited because of poor engraftment of human CML-LICs in NOD-SCID mice and nonphysiologic expression of oncogenes in retroviral transduction mouse models. To address these challenges, we generated mice bearing conditional knockin alleles of two human oncogenes: HIP1/PDGFbetaR (H/P) and AML1-ETO (A/E). Unlike retroviral transduction, physiologic expression of H/P or A/E individually failed to induce disease, but coexpression of both H/P and A/E led to rapid onset of a fully penetrant, myeloproliferative disorder, indicating cooperativity between these two alleles. Although imatin","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 Aug","modification":"2025-06-01T12:36:21.115Z","creation":"2019-03-27T00:25:58Z"},"accession":"S-EPMC2763369","cross_references":{"pubmed":["19647224"],"doi":["10.1016/j.ccr.2009.06.007"]}}