{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:28:56Z","timestamp":1789691336656,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T00:00:00Z","timestamp":1522195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004376","name":"Terry Fox Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004376","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (\u223c10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60%\u201070% of cases and include <jats:italic>RBM15\u2010MKL1<\/jats:italic>, <jats:italic>CBFA2T3\u2010GLIS2<\/jats:italic>, <jats:italic>NUP98\u2010KDM5A<\/jats:italic> and <jats:italic>MLL<\/jats:italic> rearrangements. In addition, another 4% of AMKL harbor <jats:italic>NUP98<\/jats:italic> rearrangements (<jats:italic>NUP98<\/jats:italic>r), with yet undetermined fusion partners. We report a novel <jats:italic>NUP98\u2010BPTF<\/jats:italic> fusion in an infant presenting with primary refractory AMKL. In this <jats:italic>NUP98<\/jats:italic>r, the C\u2010terminal chromatin recognition modules of BPTF, a core subunit of the NURF (nucleosome remodeling factor) ATP\u2010dependent chromatin\u2010remodeling complex, are fused to the N\u2010terminal moiety of NUP98, creating an in frame NUP98\u2010BPTF fusion, with structural homology to NUP98\u2010KDM5A. The leukemic blasts expressed two NUP98\u2010BPTF splicing variants, containing one or two tandemly spaced PHD chromatin reader domains. Our study also identified an unreported wild type BPTF splicing variant encoding for 2 PHD domains, detected both in normal cord blood CD34<jats:sup>+<\/jats:sup> cells and in leukemic blasts, as with the fly BPTF homolog, Nurf301. Disease course was marked by rapid progression and primary chemoresistance, with ultimately significant tumor burden reduction following treatment with a clofarabine containing regimen. In sum, we report 2 novel NUP98\u2010BPTF fusion isoforms that contribute to refine the <jats:italic>NUP98<\/jats:italic>r subgroup of pediatric AMKL. Multicenter clinical trials are critically required to determine the frequency of this fusion in AMKL patients and explore innovative treatment strategies for a disease still plagued with poor outcomes.<\/jats:p>","DOI":"10.1002\/gcc.22532","type":"journal-article","created":{"date-parts":[[2018,2,10]],"date-time":"2018-02-10T15:52:40Z","timestamp":1518277960000},"page":"311-319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["<i>NUP98\u2010BPTF<\/i> gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy"],"prefix":"10.1002","volume":"57","author":[{"given":"Mathieu","family":"Roussy","sequence":"first","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Biomedical Sciences Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Bilodeau","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loubna","family":"Jouan","sequence":"additional","affiliation":[{"name":"Integrated Centre for Pediatric Clinical Genomics CHU Sainte\u2010Justine Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Tibout","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Laram\u00e9e","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Lemyre","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Cytogenetics laboratory, genetics division CHU Sainte\u2010Justine Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"L\u00e9veill\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Cytogenetics laboratory, genetics division CHU Sainte\u2010Justine Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Tihy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Cytogenetics laboratory, genetics division CHU Sainte\u2010Justine Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Cardin","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Sauvageau","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Couture","sequence":"additional","affiliation":[{"name":"Molecular diagnostic laboratory CHU Sainte\u2010Justine Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Louis","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Choblet","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Patey","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Pathology CHU Sainte\u2010Justine Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Gendron","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, Institute for Research in Immunology and Cancer (IRIC), Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Duval","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Teira","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9e","family":"H\u00e9bert","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Division of Hematology Maisonneuve\u2010Rosemont Hospital Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Qu\u00e9bec Leukemia Cell Bank Maisonneuve\u2010Rosemont Hospital Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Institute for Research in Immunology and Cancer (IRIC), Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Institute for Research in Immunology and Cancer (IRIC), Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Laboratory for high throughput biology IRIC, Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja A.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital Memphis Tennessee"},{"name":"Department of Oncology St. Jude Children's Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique","family":"Bittencourt","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5364-5924","authenticated-orcid":false,"given":"Sonia","family":"Cellot","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Division Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Qu\u00e9bec Leukemia Cell Bank Maisonneuve\u2010Rosemont Hospital Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2017.07.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-05-567859"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121343"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.10.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.87"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)11009-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm404"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1344"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1129"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0939-7"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3772"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2017.1360836"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.09.003"},{"key":"e_1_2_7_15_1","first-page":"364","article-title":"The PHD finger: A versatile epigenome reader","volume":"36","author":"Sanchez R","year":"2011","journal-title":"Trends Biochem Sci."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24789"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-328880"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.267"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-346643"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-04-570929"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08036"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.053"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04815"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000241"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.10.001"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.04.031"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10153"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3535"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1216-1587a"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4439"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-604496"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3947"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22532","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T15:20:43Z","timestamp":1695568843000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,28]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/gcc.22532"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22532","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,28]]},"assertion":[{"value":"2018-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}