De novo UBE2A mutations are recurrently acquired during chronic myeloid leukemia progression and interfere with myeloid differentiation pathways

Vera Magistroni, Mario Mauri, Deborah D'Aliberti, Caterina Mezzatesta, Ilaria Crespiatico, Miriam Nava, Diletta Fontana, Nitesh Sharma, Wendy Parker, Andreas Schreiber, David Yeung, Alessandra Pirola, Sara Readelli, Luca Massimino, Paul Wang, Praveen Khandelwal, Stefania Citterio, Michela Viltadi, Silvia Bombelli, Roberta RigolioRoberto Perego, Jacqueline Boultwood, Alessandro Morotti, Giuseppe Saglio, Dong Wook Kim, Susan Branford, Carlo Gambacorti-Passerini, Rocco Piazza1

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Despite the advent of tyrosine kinase inhibitors, a proportion of chronic myeloid leukemia patients in chronic phase fail to respond to imatinib or to second-generation inhibitors and progress to blast crisis. Until now, improvements in the understanding of the m olecular mechanism s res ponsib l e for c hronic myeloid leukemia transformation from chronic phase to the aggressive blast crisis remain limited. Here we present a large parallel sequencing analysis of 10 blast crisis samples and of the corresponding autologous chronic phase controls that reveals, for the first time, recurrent mutations affecting the ubiquitin-conjugating enzyme E2A gene (UBE2A, formerly RAD6A). Additional analyses on a cohort of 24 blast crisis, 41 chronic phase as well as 40 acute myeloid leukemia and 38 atypical chronic myeloid leukemia patients at onset confirmed that UBE2A mutations are specifically acquired during chronic myeloid leukemia progression, with a frequency of 16.7% in advanced phases. In vitro studies show that the mutations here described cause a decrease in UBE2A activity, leading to an impairment of myeloid differentiation in chronic myeloid leukemia cells.

Original languageEnglish
Pages (from-to)1789-1797
Number of pages9
Issue number9
Publication statusPublished or Issued - 31 Aug 2019

ASJC Scopus subject areas

  • Hematology

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