title: Erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a myeloproliferative disease in mice.
abstract: The JAK2V617F mutation has been found in most cases of Ph-negative myeloproliferative neoplasms. Recent studies have shown that expression of Jak2V617F in the hematopoietic compartment causes marked expansion of erythroid progenitors and their transformation to cytokine-independence. To determine if erythroid progenitors are the target cells for induction and propagation of Jak2V617F-evoked myeloproliferative neoplasm, we used a conditional Jak2V617F knock-in mouse and an erythroid-lineage specific EpoRCre line. Erythroid-specific expression of heterozygous or homozygous Jak2V617F resulted in a polycythemia-like phenotype characterized by increase in hematocrit and hemoglobin, increased red blood cells, erythropoietin-independent erythroid colonies and splenomegaly. Transplantation of Jak2V617F-expressing erythroid progenitors from the diseased mice into secondary recipients could not propagate the disease. Our results suggest that erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a polycythemia-like disease in a gene-dose dependent manner. Jak2V617F mutation, however, does not confer leukemia stem cell-like properties to erythroid progenitors.
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
authors.forename: Hajime
authors.initials: H
authors.lastname: Akada
authors.forename: Saeko
authors.initials: S
authors.lastname: Akada
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hutchison
authors.forename: Golam
authors.initials: G
authors.lastname: Mohi
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019426:Integrases / Q000378:metabolism; D053614:Janus Kinase 2 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology*; D011086:Polycythemia / Q000209:etiology* / Q000473:pathology; D017467:Receptors, Erythropoietin / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017467:Receptors, Erythropoietin; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; C045073:Cre recombinase; D019426:Integrases