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We investigated the potential association between the degree of involvement of BM hematopoiesis by the <jats:italic>KIT<\/jats:italic> D816V mutation and the distribution of different maturation\u2010associated compartments of bone marrow (BM) and peripheral blood (PB) CD34<jats:sup>+<\/jats:sup> hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The distribution of different maturation\u2010associated subsets of BM and PB CD34<jats:sup>+<\/jats:sup> HPC from 64 newly diagnosed (<jats:italic>KIT<\/jats:italic>\u2010mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS\u2010purified PB cell compartments were also investigated for the <jats:italic>KIT<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ISM patients showed higher percentages of both BM and PB MC\u2010committed CD34<jats:sup>+<\/jats:sup> HPC vs controls, particularly among ISM cases with MC\u2010restricted <jats:italic>KIT<\/jats:italic> mutation (ISM<jats:sub>MC<\/jats:sub>); this was associated with progressive blockade of maturation of CD34<jats:sup>+<\/jats:sup> HPC to the neutrophil lineage from ISM<jats:sub>MC<\/jats:sub> to multilineage <jats:italic>KIT<\/jats:italic>\u2010mutated cases (ISM<jats:sub>ML<\/jats:sub>). Regarding the frequency of <jats:italic>KIT<\/jats:italic>\u2010mutated cases and cell populations in PB, variable patterns were observed, the percentage of <jats:italic>KIT<\/jats:italic>\u2010mutated PB CD34<jats:sup>+<\/jats:sup> HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs\u2212<jats:sub>MC<\/jats:sub> and ISMs+<jats:sub>MC<\/jats:sub> to ISM<jats:sub>ML<\/jats:sub> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The presence of the <jats:italic>KIT<\/jats:italic> D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34<jats:sup>+<\/jats:sup> HPC and multiple myeloid cell subpopulations, <jats:italic>KIT<\/jats:italic>\u2010mutated PB CD34<jats:sup>+<\/jats:sup> HPC potentially contributing to early dissemination of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13413","type":"journal-article","created":{"date-parts":[[2018,1,13]],"date-time":"2018-01-13T13:48:23Z","timestamp":1515851303000},"page":"1294-1304","source":"Crossref","is-referenced-by-count":14,"title":["Characterization of CD34<sup>+<\/sup> hematopoietic cells in systemic mastocytosis: Potential role in disease dissemination"],"prefix":"10.1111","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-7398","authenticated-orcid":false,"given":"A.","family":"Mayado","sequence":"first","affiliation":[{"name":"Cancer Research Centre (IBMCC USAL\u2010CSIC) Cytometry Service (NUCLEUS) and Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"},{"name":"Biomedical Research Networking Centre Consortium\u2013CIBER\u2010CIBERONC of the Institute of Health Carlos III Madrid Spain"},{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Teodosio","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Dasilva\u2010Freire","sequence":"additional","affiliation":[{"name":"Cancer Research Centre (IBMCC USAL\u2010CSIC) Cytometry Service (NUCLEUS) and Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"},{"name":"Biomedical Research Networking Centre Consortium\u2013CIBER\u2010CIBERONC of the Institute of Health Carlos III Madrid Spain"},{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Jara\u2010Acevedo","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"},{"name":"Sequencing DNA Service (NUCLEUS) University of Salamanca Salamanca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. C.","family":"Garcia\u2010Montero","sequence":"additional","affiliation":[{"name":"Cancer Research Centre (IBMCC USAL\u2010CSIC) Cytometry Service (NUCLEUS) and Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"},{"name":"Biomedical Research Networking Centre Consortium\u2013CIBER\u2010CIBERONC of the Institute of Health Carlos III Madrid Spain"},{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"\u00c1lvarez\u2010Twose","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast) Hospital Virgen del Valle Toledo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"S\u00e1nchez\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast) Hospital Virgen del Valle Toledo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Matito","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast) Hospital Virgen del Valle Toledo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Caldas","sequence":"additional","affiliation":[{"name":"Cancer Research Centre (IBMCC USAL\u2010CSIC) Cytometry Service (NUCLEUS) and Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"},{"name":"Biomedical Research Networking Centre Consortium\u2013CIBER\u2010CIBERONC of the Institute of Health Carlos III Madrid Spain"},{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. I.","family":"Mu\u00f1oz\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Cancer Research Centre (IBMCC USAL\u2010CSIC) Cytometry Service (NUCLEUS) and Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"},{"name":"Biomedical Research Networking Centre Consortium\u2013CIBER\u2010CIBERONC of the Institute of Health Carlos III Madrid Spain"},{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Henriques","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis (REMA) Toledo Salamanca Spain"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast) Hospital Virgen del Valle Toledo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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