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Both types of iPSCs fulfilled the quality criteria. Mutated iPSC colonies generated significantly more CD34<jats:sup>+<\/jats:sup> and CD34<jats:sup>+<\/jats:sup>CD45<jats:sup>+<\/jats:sup> cells compared to non\u2010mutated iPSC colonies in a culture coated with irradiated AGM\u2010S3 cells to which four growth factors were added sequentially or simultaneously. The haematopoietic differentiation potential of non\u2010mutated JMML iPSC colonies was similar to or lower than that of iPSC colonies from a healthy individual. The <jats:italic>PTPN11<\/jats:italic> mutation coexisted with the <jats:italic>OSBP2<\/jats:italic> c.389C&gt;T mutation. Zinc\u2010finger nuclease\u2010mediated homologous recombination revealed that correction of <jats:italic>PTPN11<\/jats:italic> mutation in iPSCs with <jats:italic>PTPN11<\/jats:italic> and <jats:italic>OSBP2<\/jats:italic> mutations resulted in reduced CD34<jats:sup>+<\/jats:sup> cell generation to a level similar to that obtained with JMML iPSC colonies with the wild\u2010type of both genes, and interestingly, to that obtained with normal iPSC colonies. Transduction of the <jats:italic>PTPN11<\/jats:italic> mutation into JMML iPSCs with the wild\u2010type of both genes increased CD34<jats:sup>+<\/jats:sup> cell production to a level comparable to that obtained with JMML iPSC colonies harbouring the two genetic mutations. Thus, <jats:italic>PTPN11<\/jats:italic> mutation may be the most essential abnormality to confer an aberrant haematopoietic differentiation potential in this disorder.<\/jats:p>","DOI":"10.1111\/bjh.16060","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T01:35:02Z","timestamp":1561080902000},"page":"163-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Essential role of <i>PTPN11<\/i> mutation in enhanced haematopoietic differentiation potential of induced pluripotent stem cells of juvenile myelomonocytic leukaemia"],"prefix":"10.1111","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-2526","authenticated-orcid":false,"given":"Tomonari","family":"Shigemura","sequence":"first","affiliation":[{"name":"Department of Paediatrics Shinshu University School of Medicine Matsumoto 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengming","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Organ Technology, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering Shinshu University Graduate School of Medicine Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-6986","authenticated-orcid":false,"given":"Yasuhiro","family":"Ebihara","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, International Medical Centre Saitama Medical University Hidaka 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