{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tarnawsky SP"],"funding":["NHLBI NIH HHS","NCI NIH HHS","the U.S. National Institutes of Health","the IU Simon Cancer Centre","NIGMS NIH HHS"],"pagination":["1001-1014"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5828034"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["246(12)"],"pubmed_abstract":["<h4>Background</h4>Accumulating evidence suggests the origin of juvenile myelomonocytic leukemia (JMML) is closely associated with fetal development. Nevertheless, the contribution of embryonic progenitors to JMML pathogenesis remains unexplored. We hypothesized that expression of JMML-initiating PTPN11 mutations in HSC-independent yolk sac erythromyeloid progenitors (YS EMPs) would result in a mouse model of pediatric myeloproliferative neoplasm (MPN).<h4>Results</h4>E9.5 YS EMPs from VavCre+;PTPN11<sup>D61Y</sup> embryos demonstrated growth hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and hyperactive RAS-ERK signaling. Mutant EMPs engrafted the spleens of neonatal recipients, but did not cause disease. To assess MPN development during unperturbed hematopo"],"journal":["Developmental dynamics : an official publication of the American Association of Anatomists"],"pubmed_title":["Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice."],"pmcid":["PMC5828034"],"funding_grant_id":["T32 GM077229","2289903","F30 CA210518","F30 HL128011","CA202296","R21 CA202296","P30 CA082709"],"pubmed_authors":["Chan RJ","Tarnawsky SP","Deng L","Yoshimoto M","Yoder MC"],"additional_accession":[]},"is_claimable":false,"name":"Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice.","description":"<h4>Background</h4>Accumulating evidence suggests the origin of juvenile myelomonocytic leukemia (JMML) is closely associated with fetal development. Nevertheless, the contribution of embryonic progenitors to JMML pathogenesis remains unexplored. We hypothesized that expression of JMML-initiating PTPN11 mutations in HSC-independent yolk sac erythromyeloid progenitors (YS EMPs) would result in a mouse model of pediatric myeloproliferative neoplasm (MPN).<h4>Results</h4>E9.5 YS EMPs from VavCre+;PTPN11<sup>D61Y</sup> embryos demonstrated growth hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and hyperactive RAS-ERK signaling. Mutant EMPs engrafted the spleens of neonatal recipients, but did not cause disease. To assess MPN development during unperturbed hematopo","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Dec","modification":"2025-04-21T20:12:47.167Z","creation":"2019-03-27T00:09:26Z"},"accession":"S-EPMC5828034","cross_references":{"pubmed":["28975680"],"doi":["10.1002/dvdy.24598"]}}