{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:43:29Z","timestamp":1788864209289,"version":"build-2803163510"},"reference-count":102,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"27","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Primary plasma cell leukemia (pPCL) is an aggressive subtype of multiple myeloma, which is distinguished from newly diagnosed multiple myeloma (NDMM) on the basis of the presence of \u2265 20% circulating tumor cells (CTCs). A molecular marker for pPCL is currently lacking, which could help identify NDMM patients with high-risk PCL-like disease, despite not having been recognized as such clinically. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> A transcriptomic classifier for PCL-like disease was bioinformatically constructed and validated by leveraging information on baseline CTC levels, tumor burden, and tumor transcriptomics from 154 patients with NDMM included in the Cassiopeia or HO143 trials and 29 patients with pPCL from the EMN12\/HO129 trial. Its prognostic value was assessed in an independent cohort of 2,139 patients with NDMM from the HOVON-65\/GMMG-HD4, HOVON-87\/NMSG-18, EMN02\/HO95, MRC-IX, Total Therapy 2, Total Therapy 3, and MMRF CoMMpass studies. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> High CTC levels were associated with the expression of 1,700 genes, independent of tumor burden (false discovery rate &lt; 0.05). Of these, 54 genes were selected by leave-one-out cross-validation to construct a transcriptomic classifier representing PCL-like disease. This not only demonstrated a sensitivity of 93% to identify pPCL in the validation cohort but also classified 10% of NDMM tumors as PCL-like. PCL-like MM transcriptionally and cytogenetically resembled pPCL, but presented with significantly lower CTC levels and tumor burden. Multivariate analyses in NDMM confirmed the significant prognostic value of PCL-like status in the context of Revised International Staging System stage, age, and treatment, regarding both progression-free (hazard ratio, 1.64; 95% CI, 1.30 to 2.07) and overall survival (hazard ratio, 1.89; 95% CI, 1.42 to 2.50). <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> pPCL was identified on the basis of a specific tumor transcriptome, which was also present in patients with high-risk NDMM, despite not being clinically leukemic. Incorporating PCL-like status into current risk models in NDMM may improve prognostic accuracy. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.01217","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T19:59:27Z","timestamp":1648756767000},"page":"3132-3150","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":37,"title":["Identification of High-Risk Multiple Myeloma With a Plasma Cell Leukemia-Like Transcriptomic Profile"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1296-120X","authenticated-orcid":false,"given":"Davine","family":"Hofste op Bruinink","sequence":"first","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"},{"name":"Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-1762","authenticated-orcid":false,"given":"Rowan","family":"Kuiper","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"},{"name":"SkylineDx, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6648-8171","authenticated-orcid":false,"given":"Mark","family":"van Duin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-4273","authenticated-orcid":false,"given":"Tom","family":"Cupedo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-3763","authenticated-orcid":false,"given":"Vincent H.J.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-6455","authenticated-orcid":false,"given":"Remco","family":"Hoogenboezem","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-2671","authenticated-orcid":false,"given":"Bronno","family":"van der Holt","sequence":"additional","affiliation":[{"name":"HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2280-7617","authenticated-orcid":false,"given":"H. Berna","family":"Beverloo","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1640-0119","authenticated-orcid":false,"given":"Erik T.","family":"Valent","sequence":"additional","affiliation":[{"name":"SkylineDx, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-9376","authenticated-orcid":false,"given":"Michael","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-412X","authenticated-orcid":false,"given":"Francesca","family":"Gay","sequence":"additional","affiliation":[{"name":"Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Citt\u00e0 della Salute e della Scienza di Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-8003","authenticated-orcid":false,"given":"Annemiek","family":"Broijl","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3050-0140","authenticated-orcid":false,"given":"Herv\u00e9","family":"Avet-Loiseau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9nomique du My\u00e9lome, IUC-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7344-9795","authenticated-orcid":false,"given":"Nikhil C.","family":"Munshi","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-6594","authenticated-orcid":false,"given":"Pellegrino","family":"Musto","sequence":"additional","affiliation":[{"name":"\u201cAldo Moro\u201d University School of Medicine, Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-8746","authenticated-orcid":false,"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital H\u00f4tel-Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-1820","authenticated-orcid":false,"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels W.C.J.","family":"van de Donk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2237","authenticated-orcid":false,"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","first-page":"336","volume":"19","author":"Gluzinski A","year":"1906","journal-title":"Wien Klin Wochenschr"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0153-9"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S99463"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.133.5.813"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-019-0754-x"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.63"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-408682"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.336"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0209-7"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-014-2211-0"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.158303"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0140-1"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.107"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3461"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-020-0336-z"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-019-0253-1"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4028"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2043"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.07.003"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7442"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-139340"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2018.09.007"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.4"},{"key":"b24","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1182\/blood.V97.3.822","volume":"97","author":"Avet-Loiseau H","year":"2001","journal-title":"Blood"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.176"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2004.05.004"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2008.06.027"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20670"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23339"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31240-1"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03143"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-125120"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.6820"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679415"},{"key":"b35","doi-asserted-by":"crossref","first-page":"e456","DOI":"10.1016\/S2352-3026(20)30099-5","volume":"7","author":"Cavo M","year":"2020","journal-title":"Lancet Haematol"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1007\/BF03165280"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06639.x"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-338665"},{"key":"b39","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.043372"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.29"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.267831"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-631200"},{"key":"b43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"b44","doi-asserted-by":"publisher","DOI":"10.1038\/nature08460"},{"key":"b45","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.127"},{"key":"b46","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-038430"},{"key":"b47","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0196-8"},{"key":"b48","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"b49","doi-asserted-by":"publisher","DOI":"10.1136\/ebmental-2019-300117"},{"key":"b50","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.2267"},{"key":"b51","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.242"},{"key":"b52","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401211"},{"key":"b53","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01362-5"},{"key":"b54","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.7.2528"},{"key":"b55","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0015-0"},{"key":"b56","first-page":"325","volume":"23","author":"Rimkus T","year":"2017","journal-title":"Discov Med"},{"key":"b57","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.161"},{"key":"b58","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1802"},{"key":"b59","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2004.01.008"},{"key":"b60","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.088"},{"key":"b61","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1128"},{"key":"b62","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2014.06.003"},{"key":"b63","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3043"},{"key":"b64","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.003"},{"key":"b65","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00309-9"},{"key":"b66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2015654118"},{"key":"b67","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.3.1032"},{"key":"b68","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403647"},{"key":"b69","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-380410"},{"key":"b70","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05058-y"},{"key":"b71","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00437"},{"key":"b72","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.4659"},{"key":"b73","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.98"},{"key":"b74","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25709"},{"key":"b75","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13484"},{"key":"b76","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000404"},{"key":"b77","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-137075"},{"key":"b78","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-1858"},{"key":"b79","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-510453"},{"key":"b80","doi-asserted-by":"publisher","DOI":"10.1007\/s12308-018-0335-1"},{"key":"b81","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0660-0"},{"key":"b82","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17459-z"},{"key":"b83","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.004"},{"key":"b84","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04428.x"},{"key":"b85","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.e20510"},{"key":"b86","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.1929"},{"key":"b87","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.241"},{"key":"b88","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31718"},{"key":"b89","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0059-6"},{"key":"b90","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15092"},{"key":"b91","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0830-0"},{"key":"b92","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2020.05.014"},{"key":"b93","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.08.035"},{"key":"b94","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160817514"},{"key":"b95","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12533"},{"key":"b96","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.6115"},{"key":"b97","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-139559"},{"key":"b98","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12986"},{"key":"b99","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25331"},{"key":"b100","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0958-y"},{"key":"b101","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000578"},{"key":"b102","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402114"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.21.01217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:00:09Z","timestamp":1663279209000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.01217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":102,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2022,9,20]]}},"alternative-id":["10.1200\/JCO.21.01217"],"URL":"https:\/\/doi.org\/10.1200\/jco.21.01217","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]},"assertion":[{"value":"2021-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}