Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice

dc.contributor.authorTarnawsky, Stefan P.
dc.contributor.authorYoshimoto, Momoko
dc.contributor.authorDeng, Lisa
dc.contributor.authorChan, Rebecca J.
dc.contributor.authorYoder, Mervin C.
dc.contributor.departmentPediatrics, School of Medicineen_US
dc.date.accessioned2017-11-21T16:21:02Z
dc.date.available2017-11-21T16:21:02Z
dc.date.issued2017-12
dc.description.abstractBackground: 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). Results: E9.5 YS EMPs from VavCre+;PTPN11D61Y 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 hematopoiesis we generated CSF1R-MCM+;PTPN11E76K;ROSAYFP mice in which oncogene expression was restricted to EMPs. Yellow fluorescent protein-positive progeny of mutant EMPs persisted in tissues one year after birth and demonstrated hyperactive RAS-ERK signaling. Nevertheless, these mice had normal survival and did not demonstrate features of MPN. Conclusions: YS EMPs expressing mutant PTPN11 demonstrate functional and molecular features of JMML but do not cause disease following transplantation nor following unperturbed development.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationTarnawsky, S. P., Yoshimoto, M., Deng, L., Chan, R. J. and Yoder, M. C. (2017), Yolk Sac Erythromyeloid Progenitors Expressing Gain Of Function PTPN11 Have Functional Features Of JMML But Are Not Sufficient To Cause Disease In Mice. Dev. Dyn., 246(12), 1001-1014. http://dx.doi.org/10.1002/dvdy.24598en_US
dc.identifier.urihttps://hdl.handle.net/1805/14633
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.isversionof10.1002/dvdy.24598en_US
dc.relation.journalDevelopmental Dynamicsen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectJuvenile Myelomonocytic Leukemiaen_US
dc.subjectfetal developmenten_US
dc.subjectembryonic progenitorsen_US
dc.titleYolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in miceen_US
dc.typeArticleen_US
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