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A number of conditional mouse models of\n                    <jats:italic>JAK2<\/jats:italic>\n                    \u2010V617F\u2010driven MPN have been generated that rely on Cre\u2010LoxP\u2010mediated activation, resulting in polyclonal disease. To more closely mimic the monoclonal origin of human MPN, transplantations of single purified\n                    <jats:italic>JAK2<\/jats:italic>\n                    \u2010mutant HSCs or bone marrow (BM) at limiting dilutions into lethally irradiated recipient mice have been previously performed. However, irradiation is known to alter the BM microenvironment and also to induce transient aplasia accompanied by elevated cytokine levels that promote the expansion of the mutant clone. To overcome these limitations, we examined whether\n                    <jats:italic>JAK2\u2010<\/jats:italic>\n                    V617F\u2010mutant HSCs are able to engraft and initiate MPN in non\u2010conditioned recipients. We found that BM from two different MPN models, one expressing the human\n                    <jats:italic>JAK2<\/jats:italic>\n                    \u2010V617F, and another expressing the mouse\n                    <jats:italic>Jak2<\/jats:italic>\n                    \u2010V617F, efficiently engrafted and initiated MPN in non\u2010irradiated immunocompromised\n                    <jats:italic>Rag2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    recipients. MPN evolved even in transplantations at limiting dilutions, showing the high competitiveness of single\n                    <jats:italic>JAK2<\/jats:italic>\n                    \u2010mutant HSCs. In contrast, BM from mice expressing the human\n                    <jats:italic>JAK2<\/jats:italic>\n                    \u2010V617F failed to engraft in non\u2010conditioned immunocompetent C57BL\/6 mice, while BM from mice expressing the mouse\n                    <jats:italic>Jak2<\/jats:italic>\n                    \u2010V617F engrafted and initiated MPN, suggesting that mouse JAK2\u2010V617F protein, which differs from the endogenous JAK2 in only one amino acid, was tolerated. Our results show that\n                    <jats:italic>JAK2<\/jats:italic>\n                    \u2010V617F mutant HSCs can outcompete resident non\u2010mutated HSCs even in the absence of elevated cytokine levels and without the need of emptying stem cell niches by irradiation.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70359","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:22:17Z","timestamp":1777378937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A single\n                    <i>JAK2<\/i>\n                    \u2010V617F hematopoietic stem cell can initiate myeloproliferative neoplasm when transplanted into non\u2010conditioned recipient mice"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1999-782X","authenticated-orcid":false,"given":"Quentin","family":"Kimmerlin","sequence":"first","affiliation":[{"name":"Baylor College of Medicine Dan L Duncan Comprehensive Cancer Center Houston Texas USA"},{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6374-2201","authenticated-orcid":false,"given":"Morgane","family":"Hilpert","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4556-5557","authenticated-orcid":false,"given":"Nils","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-4615","authenticated-orcid":false,"given":"Alexandre","family":"Guy","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4575-8029","authenticated-orcid":false,"given":"Marc","family":"Usart","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine Dan L Duncan Comprehensive Cancer Center Houston Texas USA"},{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-2856","authenticated-orcid":false,"given":"Jan","family":"Stetka","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-5017","authenticated-orcid":false,"given":"Patryk","family":"Sobieralski","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine Dan L Duncan Comprehensive Cancer Center Houston Texas USA"},{"name":"Department of Hematology and Transplantology Medical University of Gda\u0144sk Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"Almeida Fonseca","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Experimental Hematology University Hospital Basel and 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