2017
DOI: 10.1002/dvdy.24598
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Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice

Abstract: Background 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 demonstrat… Show more

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Cited by 7 publications
(10 citation statements)
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References 79 publications
(120 reference statements)
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“…First, post-transplant hematopoiesis is markedly different from unperturbed hematopoiesis. Transplanted progenitors have altered lifespans, biased differentiation potentials, and frequently give rise to different disease manifestations when compared with progenitors in non-transplanted hosts [ 15 17 ]. Second, whereas somatic JMML mutations are restricted to hematopoietic cells, the majority of Cre stains used in the study of JMML have promiscuous tissue activity.…”
Section: Introductionmentioning
confidence: 99%
“…First, post-transplant hematopoiesis is markedly different from unperturbed hematopoiesis. Transplanted progenitors have altered lifespans, biased differentiation potentials, and frequently give rise to different disease manifestations when compared with progenitors in non-transplanted hosts [ 15 17 ]. Second, whereas somatic JMML mutations are restricted to hematopoietic cells, the majority of Cre stains used in the study of JMML have promiscuous tissue activity.…”
Section: Introductionmentioning
confidence: 99%
“…For this purpose, the ptpn11 gain-of-function JMML-initiating mutation had been introduced into EMPs. Although mice demonstrated features of JMML and mutant EMPs engrafted spleens of neonatal recipients, the disease was not transplantable ( Tarnawsky et al, 2017 ).…”
Section: An Hsc-independent Origin Of Pediatric Leukemia?mentioning
confidence: 99%
“…These evidences suggested a fetal origin for JMML, confirmed by the retrospective analysis of JMML patient samples collected at birth ( Kratz et al, 2005 ; Matsuda et al, 2010 ; Stieglitz et al, 2015 ). However, yolk sac EMPs expressing gain of function PTPN11 mutations recapitulate part of the characteristics of JMML, but they are not able to cause disease in mice ( Tarnawsky et al, 2017 ). Recently, gene expression profiling of JMML samples identified a subgroup characterized by high LIN28B expression and higher HbF levels ( Helsmoortel et al, 2016b ).…”
Section: Inappropriate Timing Of γ-Globin Expression In “Fetal-type” mentioning
confidence: 99%