Here, we report that hematopoietic cells differentiated from human induced pluripotent stem cells (hiPSCs) harboring NS/JMML-causing PTPN11 mutations recapitulated JMML features. hiPSC-derived NS/JMML myeloid cells exhibited increased signaling through STAT5 and upregulation of miR-223 and miR-15a.
We recently demonstrated that somatic PTPN11 mutations are the most frequent lesion in juvenile myelomonocytic leukemia and are observed in a smaller percentage of children with other myeloid malignancies.
Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia.
Transduction of the PTPN11 mutation into JMML iPSCs with the wild-type of both genes increased CD34<sup>+</sup> cell production to a level comparable to that obtained with JMML iPSC colonies harbouring the two genetic mutations.
Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.
Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature.
Mutations in PTPN11, the gene encoding the protein tyrosine phosphatase Shp2, are common in juvenile myelomonocytic leukemia and induce hyperactivation of the phosphoinositide-3-kinase pathway.
Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
This report describes a juvenile myelomonocytic leukemia (JMML) case with a typical PTPN11 mutation (p.E76K) at different allele frequencies in the bone marrow mononuclear cells, buccal smear cells, and fingernails at diagnosis, which was suggestive of PTPN11 somatic mosaicism; however, the PTPN11 mutation in the buccal smear cells and fingernails was lost after unrelated cord blood transplantation.