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Oncol Lett. 2016 Nov;12(5):3123-3126. Epub 2016 Sep 1.

The targetable role of herpes virus-associated ubiquitin-specific protease (HAUSP) in p190 BCR-ABL leukemia.

Author information

1
Department of Clinical and Biological Sciences, 'San Luigi Gonzaga' University Hospital, School of Medicine, University of Turin, 10043 Turin, Italy.
2
Department of Oncology, 'San Luigi Gonzaga' University Hospital, School of Medicine, University of Turin, 10043 Turin, Italy.

Abstract

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability. Notably, the inhibition of HAUSP with small molecule inhibitors promoted the upregulation of p53 protein levels. These results suggest that HAUSP inhibitors may harbor clinically relevant implications in the treatment of Ph+ ALL.

KEYWORDS:

BCR-ABL; acute lymphoblastic leukemia; herpesvirus-associated ubiquitin-specific protease; herpesvirus-associated ubiquitin-specific protease inhibitors; p190; p53

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