{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:16:11Z","timestamp":1791353771231,"version":"4.3.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,9,14]]},"abstract":"<jats:p>\n                    Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9 and 22 and giving rise to the constitutively active tyrosine kinase P210 BCR\/ABL1. Therapeutic strategies aiming for a cure of CML will require full eradication of Ph chromosome-positive (Ph\n                    <jats:sup>+<\/jats:sup>\n                    ) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells and also in cord blood CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells as a consequence of retroviral\n                    <jats:italic>BCR\/ABL1<\/jats:italic>\n                    expression. To test whether IL1RAP expression distinguishes normal (Ph\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) and leukemic (Ph\n                    <jats:sup>+<\/jats:sup>\n                    ) cells within the CML CD34\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>\u2212<\/jats:sup>\n                    cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate their Ph-chromosome status. Interestingly, we found that the CML CD34\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>\u2212<\/jats:sup>\n                    IL1RAP\n                    <jats:sup>+<\/jats:sup>\n                    cells were Ph\n                    <jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    , whereas CML CD34\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>\u2212<\/jats:sup>\n                    IL1RAP\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells were almost exclusively Ph\n                    <jats:italic>\n                      <jats:sup>\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    . By performing long-term culture-initiating cell assays on the two cell populations, we found that Ph\n                    <jats:sup>+<\/jats:sup>\n                    and Ph\n                    <jats:sup>\u2212<\/jats:sup>\n                    candidate CML stem cells could be prospectively separated. In addition, by generating an anti-IL1RAP antibody, we provide proof of concept that IL1RAP can be used as a target on CML CD34\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells to induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies IL1RAP as a unique cell surface biomarker distinguishing Ph\n                    <jats:sup>+<\/jats:sup>\n                    from Ph\n                    <jats:sup>\u2212<\/jats:sup>\n                    candidate CML stem cells and opens up a previously unexplored avenue for therapy of CML.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1004408107","type":"journal-article","created":{"date-parts":[[2010,8,30]],"date-time":"2010-08-30T22:49:18Z","timestamp":1283208558000},"page":"16280-16285","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":165,"title":["Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein"],"prefix":"10.1073","volume":"107","author":[{"given":"Marcus","family":"J\u00e4r\u00e5s","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Johnels","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"\u00c5gerstam","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Tsapogas","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Rissler","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carin","family":"Lassen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor","family":"Olofsson","sequence":"additional","affiliation":[{"name":"Departments of bHematology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Weis","family":"Bjerrum","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Richter","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Gene Therapy, Lund University, 22184 Lund, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thoas","family":"Fioretos","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, Sk\u00e5ne University Hospital, Lund University, 22185 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,8,30]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1497","article-title":"A minute chromosome in human chronic granulocytic leukemia","volume":"132","author":"Nowel P","year":"1960","unstructured":"P Nowel, D Hungerford, A minute chromosome in human chronic granulocytic leukemia. Science 132, 1497 (1960).","journal-title":"Science"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/315758a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.10.3343"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109193"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.5745"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404609"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2947"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1483"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3693"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.018"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.045"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403649"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.5320"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/146871"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.392"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404549"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.6.1476.1476"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.3662"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1253"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.447"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12804"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.6.2162.bloodjournal8862162"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399409001215"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.4049\/jimmunol.119.3.1089","article-title":"Antibody-dependent cellular cytotoxicity against murine leukemia viral antigens: Studies with human lymphoblastoid cell lines and human peripheral lymphocytes as effector cells comparing rabbit, goat, and mouse antisera","volume":"119","author":"Peters CJ","year":"1977","unstructured":"CJ Peters, AN Theofilopoulos, Antibody-dependent cellular cytotoxicity against murine leukemia viral antigens: Studies with human lymphoblastoid cell lines and human peripheral lymphocytes as effector cells comparing rabbit, goat, and mouse antisera. J Immunol 119, 1089\u20131096 (1977).","journal-title":"J Immunol"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-057521"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.319"},{"key":"e_1_3_3_28_2","article-title":"Properties of CD34+ CML stem\/progenitor cells that correlate with different clinical responses to imatinib mesylate","author":"Jiang X","year":"2010","unstructured":"X Jiang, et al., Properties of CD34+ CML stem\/progenitor cells that correlate with different clinical responses to imatinib mesylate. Blood, doi 10.1182\/blood-2009-05-222471. (2010).","journal-title":"Blood"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.16"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2003.09.016"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705939104"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1567"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403650"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-077941"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2003.12.014"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2008.11.003"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04391.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.10.3765.bloodjournal88103765"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(01)00474-4"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1004408107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T22:17:14Z","timestamp":1685744234000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1004408107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,30]]},"references-count":40,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2010,9,14]]}},"alternative-id":["10.1073\/pnas.1004408107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1004408107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,30]]},"assertion":[{"value":"2010-08-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}