title: Generation and characterization of a JAK2V617F-containing erythroleukemia cell line.
abstract: The JAK2V617F mutation is found in the majority of patients with myeloproliferative neoplasms (MPNs). Transgenic expression of the mutant gene causes MPN-like phenotypes in mice. We have produced JAK2V617F mice with p53 null background. Some of these mice developed acute erythroleukemia. From one of these mice, we derived a cell line designated J53Z1. J53Z1 cells were stained positive for surface markers CD71 and CD117 but negative for Sca-1, TER-119, CD11b, Gr-1, F4/80, CD11c, CD317, CD4, CD8a, CD3e, B220, CD19, CD41, CD42d, NK-1.1, and FceR1. Real time PCR analyses demonstrated expressions of erythropoietin receptor EpoR, GATA1, and GATA2 in these cells. J53Z1 cells grew rapidly in suspension culture containing fetal bovine serum with a doubling time of ∼18 hours. When transplanted into C57Bl/6 mice, J53Z1 cells induced acute erythroleukemia with massive infiltration of tumor cells in the spleen and liver. J53Z1 cells were responsive to stimulation with erythropoietin and stem cell factor and were selectively inhibited by JAK2 inhibitors which induced apoptosis of the cells. Together, J53Z1 cells belong to the erythroid lineage, and they may be useful for studying the role of JAK2V617F in proliferation and differentiation of erythroid cells and for identifying potential therapeutic drugs targeting JAK2.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Wanke
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Oklahoma School of Science and Mathematics, Oklahoma City, Oklahoma, United States of America.
authors.forename: Kang
authors.initials: K
authors.lastname: Zou
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Taleah
authors.initials: T
authors.lastname: Farasyn
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Wanting Tina
authors.initials: WT
authors.lastname: Ho
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology* / Q000637:transplantation; D003433:Crosses, Genetic; D004354:Drug Screening Assays, Antitumor; D004920:Erythropoiesis / Q000187:drug effects; D020869:Gene Expression Profiling; D016158:Genes, p53; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000473:pathology
chemical_list: D016298:Hematopoietic Cell Growth Factors; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2