Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL

Research output: Contribution to journalArticle



  • Oscar Molina
  • Meritxell Vinyoles
  • Isabel Granada
  • Heleia Roca-Ho
  • Francisco Gutierrez-Agüera
  • Luis Valledor
  • Carlos Manuel López-López
  • Pablo Rodríguez-González
  • Juan Luis Trincado
  • Sofía Tirados-Menéndez
  • Paola Ballerini
  • Monique L Den Boer
  • Isabel Plensa
  • Maria Del Mar Perez-Iribarne
  • Sandra Rodriguez-Perales
  • Maria Jose Calasanz
  • Manuel Ramírez
  • Rene Rodríguez
  • Mireia Camos
  • Maria Calvo
  • Clara Bueno
  • Pablo Menendez



Original languageEnglish
Early online date22 Apr 2020
Publication statusE-pub ahead of print - 22 Apr 2020
Publication type

Research output: Contribution to journalArticle


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.

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