{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:07:26Z","timestamp":1791295646463,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>JAK2V617F and MPLW515L\/K are myeloproliferative disorder (MPD)-associated mutations. We genotyped 552 individual hematopoietic colonies obtained by CD34+ cell culture from 16 affected patients (13 JAK2V617F and 3 MPLW515L\/K) to determine (a) the proportion of colonies harboring a particular mutation in the presence or absence of cytokines, (b) the lineage distribution of endogenous colonies for each mutation, and (c) the differences (if any) in the pattern of mutation among the various MPDs, as established by genotyping of individual colonies. Genotyping analysis revealed cohabitation of mutation-negative and mutation-positive endogenous colonies in polycythemia vera as well as other MPDs. Culture of progenitor cells harboring MPLW515L\/K yielded virtually no endogenous erythroid colonies in contrast to JAK2V617F-harboring progenitor cells. The mutation pattern (i.e., relative distribution of homozygous, heterozygous, or wild-type colonies) was not a distinguishing feature among the MPDs, and MPLW515 mutations were detected in B and\/or T lymphocytes in all three patients tested. These observations suggest that clonal myelopoiesis antedates acquisition of JAK2V617F or MPLW515L\/K mutations and that the latter is acquired in a lympho-myeloid progenitor cell.<\/jats:p>\n               <jats:p>Disclosure of potential conflicts of interest is found at the end of this article.<\/jats:p>","DOI":"10.1634\/stemcells.2007-0175","type":"journal-article","created":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:49:00Z","timestamp":1180658940000},"page":"2358-2362","source":"Crossref","is-referenced-by-count":63,"title":["Extending <i>Jak2<\/i>V617F and <i>Mpl<\/i>W515 Mutation Analysis to Single Hematopoietic Colonies and B and T Lymphocytes"],"prefix":"10.1093","volume":"25","author":[{"given":"Animesh","family":"Pardanani","sequence":"first","affiliation":[{"name":"Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terra L.","family":"Lasho","sequence":"additional","affiliation":[{"name":"Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Finke","sequence":"additional","affiliation":[{"name":"Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben A.","family":"Mesa","sequence":"additional","affiliation":[{"name":"Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhett P.","family":"Ketterling","sequence":"additional","affiliation":[{"name":"Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight Gary","family":"Gilliland","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayalew","family":"Tefferi","sequence":"additional","affiliation":[{"name":"Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,1,2]]},"reference":[{"key":"2022011307293040800_bib1","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nature03546","article-title":"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera","volume":"434","author":"James","year":"2005","journal-title":"Nature"},{"key":"2022011307293040800_bib2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.0030270","article-title":"MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.","volume":"3","author":"Pikman","year":"2006","journal-title":"PLoS Med"},{"key":"2022011307293040800_bib3","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1182\/blood-2005-09-3900","article-title":"X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET\/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis","volume":"107","author":"Levine","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib4","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1182\/blood-2006-04-018879","article-title":"MPL515 mutations in myeloproliferative and other myeloid disorders: A study of 1182 patients","volume":"108","author":"Pardanani","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib5","doi-asserted-by":"crossref","first-page":"6224","DOI":"10.1073\/pnas.0601462103","article-title":"The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation","volume":"103","author":"Jamieson","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022011307293040800_bib6","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1182\/blood-2006-02-002030","article-title":"JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis","volume":"108","author":"Lacout","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib7","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1182\/blood-2005-12-4824","article-title":"Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model","volume":"107","author":"Wernig","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0000018","article-title":"Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F.","volume":"1","author":"Zaleskas","year":"2006","journal-title":"PLoS ONE"},{"key":"2022011307293040800_bib9","doi-asserted-by":"crossref","first-page":"11156","DOI":"10.1158\/0008-5472.CAN-06-2210","article-title":"Characterization of murine JAK2V617F-positive myeloproliferative disease","volume":"66","author":"Bumm","year":"2006","journal-title":"Cancer Res"},{"key":"2022011307293040800_bib10","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/sj.leu.2404214","article-title":"Essential thrombocythemias without V617F JAK2 mutation are clonal hematopoietic stem cell disorders","volume":"20","author":"Kiladjian","year":"2006","journal-title":"Leukemia"},{"key":"2022011307293040800_bib11","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1182\/blood-2005-11-009605","article-title":"Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders","volume":"108","author":"Kralovics","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib12","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/j.1365-2141.2005.05683.x","article-title":"The JAK2V617F mutation is acquired secondary to the predisposing alteration in familial polycythaemia vera","volume":"130","author":"Cario","year":"2005","journal-title":"Br J Haematol"},{"key":"2022011307293040800_bib13","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1182\/blood-2005-12-4852","article-title":"Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders","volume":"108","author":"Bellanne-Chantelot","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib14","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1182\/blood-2005-12-4988","article-title":"Discordant distribution of JAK2V617F mutation in siblings with familial myeloproliferative disorders","volume":"107","author":"Pardanani","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib15","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(05)71142-9","article-title":"Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders","volume":"365","author":"Baxter","year":"2005","journal-title":"Lancet"},{"key":"2022011307293040800_bib16","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1182\/blood-2006-04-018259","article-title":"Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia","volume":"108","author":"Scott","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib17","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1182\/blood-2002-04-1199","article-title":"The World Health Organization (WHO) classification of the myeloid neoplasms","volume":"100","author":"Vardiman","year":"2002","journal-title":"Blood"},{"key":"2022011307293040800_bib18","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/j.1365-2141.2005.05682.x","article-title":"Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes","volume":"130","author":"Lasho","year":"2005","journal-title":"Br J Haematol"},{"key":"2022011307293040800_bib19","first-page":"1207","article-title":"A standardized endogenous megakaryocytic erythroid colony assay for the diagnosis of essential thrombocythemia","volume":"89","author":"Dobo","year":"2004","journal-title":"Haematologica"},{"key":"2022011307293040800_bib20","doi-asserted-by":"crossref","first-page":"3357","DOI":"10.1182\/blood.V91.9.3357","article-title":"Highly sensitive fluorescence in situ hybridization method to detect double BCR\/ABL fusion and monitor response to therapy in chronic myeloid leukemia","volume":"91","author":"Dewald","year":"1998","journal-title":"Blood"},{"key":"2022011307293040800_bib21","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1182\/blood-2005-03-1183","article-title":"The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both \u201catypical\u201d myeloproliferative disorders and myelodysplastic syndromes","volume":"106","author":"Steensma","year":"2005","journal-title":"Blood"},{"key":"2022011307293040800_bib22","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1182\/blood.V92.6.1967","article-title":"Interleukin-10 inhibits erythropoietin-independent growth of erythroid bursts in patients with polycythemia vera","volume":"92","author":"Geissler","year":"1998","journal-title":"Blood"},{"key":"2022011307293040800_bib23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1056\/NEJMoa065202","article-title":"JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis","volume":"356","author":"Scott","year":"2007","journal-title":"N Engl J Med"},{"key":"2022011307293040800_bib24","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1182\/blood-2006-04-014712","article-title":"JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model","volume":"108","author":"Mercher","year":"2006","journal-title":"Blood"},{"key":"2022011307293040800_bib25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ccr.2006.06.002","article-title":"Activating alleles of JAK3 in acute megakaryoblastic leukemia","volume":"10","author":"Walters","year":"2006","journal-title":"Cancer Cell"},{"key":"2022011307293040800_bib26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.exphem.2006.11.012","article-title":"Polycythemia vera is not initiated by JAK2V617F mutation","volume":"35","author":"Nussenzveig","year":"2007","journal-title":"Exp Hematol"},{"key":"2022011307293040800_bib27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0301-472X(01)00789-5","article-title":"Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera","volume":"30","author":"Kralovics","year":"2002","journal-title":"Exp Hematol"},{"key":"2022011307293040800_bib28","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1365-2141.2005.05776.x","article-title":"The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: Lineage specificity and clinical correlates","volume":"131","author":"Tefferi","year":"2005","journal-title":"Br J Haematol"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1634%2Fstemcells.2007-0175","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/stemcells.2007-0175","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/stemcells.2007-0175","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/25\/9\/2358\/41965255\/stmcls_25_9_2358.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/25\/9\/2358\/41965255\/stmcls_25_9_2358.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T02:53:50Z","timestamp":1642560830000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/25\/9\/2358-2362\/6402502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,1]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2009,1,2]]},"published-print":{"date-parts":[[2007,9,1]]}},"URL":"https:\/\/doi.org\/10.1634\/stemcells.2007-0175","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2007,9,1]]},"published":{"date-parts":[[2007,9,1]]}}}