{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T21:05:47Z","timestamp":1768338347288,"version":"3.49.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, and high-hyperdiploidy (HyperD) identifies the most common subtype of pediatric B-ALL. Despite HyperD is an initiating oncogenic event affiliated to childhood B-ALL, the mitotic and chromosomal defects associated to HyperD B-ALL (HyperD-ALL) remain poorly characterized. Here, we have used 54 primary pediatric B-ALL samples to characterize the cellular-molecular mechanisms underlying the mitotic\/chromosome defects predicated to be early pathogenic contributors in HyperD-ALL. We report that HyperD-ALL blasts are low proliferative and show a delay in early mitosis at prometaphase, associated to chromosome alignment defects at the metaphase plate leading to robust chromosome segregation defects and non-modal karyotypes. Mechanistically, biochemical, functional and mass-spectrometry assays revealed that condensin complex is impaired in HyperD-ALL cells, leading to chromosome hypocondensation, loss of centromere stiffness and mis-localization of the chromosome passenger complex proteins Aurora B Kinase (AURKB) and Survivin in early mitosis. HyperD-ALL cells show chromatid cohesion defects and impaired spindle assembly checkpoint (SAC) thus undergoing mitotic slippage due to defective AURKB and impaired SAC activity, downstream of condensin complex defects. Chromosome structure\/condensation defects and hyperdiploidy were reproduced in healthy CD34+ stem\/progenitor cells upon inhibition of AURKB and\/or SAC. Collectively, hyperdiploid B-ALL is associated to defective condensin complex, AURKB and SAC.<\/jats:p>","DOI":"10.1182\/blood.2019002538","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T21:58:26Z","timestamp":1587592706000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":6,"title":["Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7585-4519","authenticated-orcid":false,"given":"Oscar","family":"Molina","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-4701","authenticated-orcid":false,"given":"Meritxell","family":"Vinyoles","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-0104","authenticated-orcid":false,"given":"Isabel","family":"Granada","sequence":"first","affiliation":[{"name":"Institut Catal\u00e0 d'Oncologia (ICO)-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leuc\u00e8mia Josep Carreras, Universitat Aut\u00f2noma de Barcelona, Badalona, Spain., BADALONA, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heleia","family":"Roca-Ho","sequence":"first","affiliation":[{"name":"IJC, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Gutierrez-Ag\u00fcera","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0636-365X","authenticated-orcid":false,"given":"Luis","family":"Valledor","sequence":"first","affiliation":[{"name":"University of Oviedo, Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Manuel","family":"L\u00f3pez-L\u00f3pez","sequence":"first","affiliation":[{"name":"University of Oviedo, Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9317-8833","authenticated-orcid":false,"given":"Pablo","family":"Rodr\u00edguez-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"University of Oviedo, Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5363-3774","authenticated-orcid":false,"given":"Juan Luis","family":"Trincado","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-1384","authenticated-orcid":false,"given":"Sof\u00eda","family":"Tirados-Men\u00e9ndez","sequence":"first","affiliation":[{"name":"Hospital Universitario Central de Asturias, Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepali","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Applied Sciences, Northumbria University. Newcastle upon Tyne., United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Ballerini","sequence":"first","affiliation":[{"name":"Service d'hematologie, Hopital Trousseau, Paris, France, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique L.","family":"Den Boer","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Plensa","sequence":"first","affiliation":[{"name":"Hospital Sant Joan de D\u00e9u Barcelona, Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria del Mar","family":"Perez-Iribarne","sequence":"first","affiliation":[{"name":"Hospital Sant Joan de D\u00e9u Barcelona, Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Rodriguez-Perales","sequence":"first","affiliation":[{"name":"CNIO, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria JOSE","family":"Calasanz","sequence":"first","affiliation":[{"name":"UNIVERSITY OF NAVARRA, Pamplona, Na, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-6973","authenticated-orcid":false,"given":"Manuel","family":"Ram\u00edrez","sequence":"first","affiliation":[{"name":"Hospital Universitario Ni\u00f1o Jes\u00fas, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-7306","authenticated-orcid":false,"given":"Rene","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Hospital Universitario Central de Asturias, Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3658-7942","authenticated-orcid":false,"given":"Mireia","family":"Camos","sequence":"first","affiliation":[{"name":"Hospital Sant Joan de Deu, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7473-0474","authenticated-orcid":false,"given":"Maria","family":"Calvo","sequence":"first","affiliation":[{"name":"Universitat de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Bueno","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Menendez","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2020,4,22]]},"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2019002538\/1724885\/blood.2019002538.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2019002538\/1724885\/blood.2019002538.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T21:58:27Z","timestamp":1587592707000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2019002538\/454450\/Impaired-Condensin-Complex-and-Aurora-B-kinase"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2019002538","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,22]]},"article-number":"blood.2019002538"}}