{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:14:02Z","timestamp":1787235242896,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Epigenetics has been shown to be relevant in oncology:\n                      <jats:italic>BMI1<\/jats:italic>\n                      overexpression has been reported in leukemias,\n                      <jats:italic>EZH2<\/jats:italic>\n                      mutations have been found in follicular lymphoma, and\n                      <jats:italic>USP22<\/jats:italic>\n                      seems to stabilize BMI1 protein. In this study, we measured the expression of\n                      <jats:italic>BMI1, EZH2<\/jats:italic>\n                      , and\n                      <jats:italic>USP22<\/jats:italic>\n                      in lymph nodes from 56 diffuse large B\u2010cell lymphoma (DLBCL) patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A new multiplex digital droplet PCR (ddPCR) has been set up to measure the expression of 4 genes (\n                      <jats:italic>BMI1, EZH2, USP22<\/jats:italic>\n                      , and\n                      <jats:italic>GAPDH<\/jats:italic>\n                      ) in the same reaction on RNA extracted from paraffin\u2010embedded tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The specificity of ddPCR was confirmed by a 100% alignment on the BLAST platform and its repeatability demonstrated by duplicates. A strict correlation between expression of\n                      <jats:italic>BMI1<\/jats:italic>\n                      and\n                      <jats:italic>EZH2<\/jats:italic>\n                      and\n                      <jats:italic>BMI1<\/jats:italic>\n                      and\n                      <jats:italic>USP22<\/jats:italic>\n                      has been found, and high expression of these genes was correlated with extra\u2010nodal lymphomas. Progression\u2010free survival (PFS) and overall survival (OS) were conditioned by IPI, bone marrow infiltration, and the complete response achievement. High levels of\n                      <jats:italic>BMI1<\/jats:italic>\n                      and\n                      <jats:italic>USP22<\/jats:italic>\n                      did not condition the response to therapy, but impaired the PFS, especially for patients defined at \u201chigh risk\u201d based on the cell of origin (no germinal center [GCB]), high BCL2 expression, and IPI 3\u20105. In this subgroup, the probability of relapse\/progression was twice higher than that of patients carrying low\n                      <jats:italic>BMI1<\/jats:italic>\n                      and\n                      <jats:italic>USP22<\/jats:italic>\n                      levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      High expression of\n                      <jats:italic>BMI1<\/jats:italic>\n                      and of\n                      <jats:italic>USP22<\/jats:italic>\n                      might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ijlh.14363","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T19:25:34Z","timestamp":1725996334000},"page":"101-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A new digital droplet\n                    <scp>PCR<\/scp>\n                    method for looking at epigenetics in diffuse large\n                    <scp>B<\/scp>\n                    \u2010cell lymphomas: The role of\n                    <scp>\n                      <i>BMI1<\/i>\n                    <\/scp>\n                    ,\n                    <scp>\n                      <i>EZH2<\/i>\n                    <\/scp>\n                    , and\n                    <scp>\n                      <i>USP22<\/i>\n                    <\/scp>\n                    genes"],"prefix":"10.1111","volume":"47","author":[{"given":"Alessio","family":"Lusci Gemignani","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robel","family":"Papotti","sequence":"additional","affiliation":[{"name":"International PhD School in Clinical and Experimental Medicine University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bomben","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco\u2010Hematology Unit Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valter","family":"Gattei","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco\u2010Hematology Unit Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche Materno\u2010Infantili e dell'Adulto Universit\u00e0 di Modena e Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Donati","sequence":"additional","affiliation":[{"name":"Pathology II Azienda Ospedaliero\u2010Universitaria Pisana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bettelli","sequence":"additional","affiliation":[{"name":"Patologia Molecolare e Medicina Predittiva, AOU Modena, Dipartimento di Scienze Mediche e Chirurgiche Materno\u2010Infantili e dell'Adulto Universit\u00e0 di Modena e Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Forti","sequence":"additional","affiliation":[{"name":"Patologia Molecolare e Medicina Predittiva, AOU Modena, Dipartimento di Scienze Mediche e Chirurgiche Materno\u2010Infantili e dell'Adulto Universit\u00e0 di Modena e Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Mansueto","sequence":"additional","affiliation":[{"name":"IRCCS\u2010CROB, Referral Cancer Center of Basilicata  Rionero in Vulture Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Di Napoli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine Sapienza University, Sant'Andrea University Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Christina","family":"Cox","sequence":"additional","affiliation":[{"name":"Haematology Department King's College Hospital NHS Trust and UOC Ematologia, AOU Sant'Andrea  Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Flenghi","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation Azienda Ospedaliera di Perugia  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Volpe","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Dardanis","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Bono","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Morganti","sequence":"additional","affiliation":[{"name":"SOD supporto statistico agli studi clinici Azienda Ospedaliero Universitaria Pisana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Sacchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche Materno\u2010Infantili e dell'Adulto Universit\u00e0 di Modena e Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4620-0038","authenticated-orcid":false,"given":"Sara","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci9010005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2021.1975188"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201003\u2010769620"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801445"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20200737"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201010\u2010606822"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200424985"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2019.1633867"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.15.35"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00555"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22088"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428\u2010013\u20101428\u2010y"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11606"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30441\u20101"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.03.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013\u2010011\u20109287\u20100"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201003455\u2010x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16445"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012\u2010022\u201009758\u20102"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c06186"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700844"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2021.106552"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2023.02.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096\u2010020\u201004076\u20103"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071738"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9051457"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20103741"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002580"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13030581"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201081577\u2010x"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25558"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035469\u2010x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/PDM.0b013e3181e202f2"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2214"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2012.05.012"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.01.005"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.533505"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2017.6136"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2666"}],"container-title":["International Journal of Laboratory Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.14363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T22:20:01Z","timestamp":1736720401000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ijlh.14363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,10]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/ijlh.14363"],"URL":"https:\/\/doi.org\/10.1111\/ijlh.14363","archive":["Portico"],"relation":{},"ISSN":["1751-5521","1751-553X"],"issn-type":[{"value":"1751-5521","type":"print"},{"value":"1751-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,10]]},"assertion":[{"value":"2023-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}