Haematologica Reports 2005; 1(issue 8): 63-66[prev][index][next]

Ubiquitin-proteasome system is a sensitive target in Ph⁺ leukemia
Martinelli G,¹ Cilloni D², Rosti G¹, Piccaluga P, Rondoni M, Bosi C , Paolini S, Pane F³, Soverini S¹
Amabile M¹, Nadali G⁴, Izzo B³, Iacobucci I¹, Poerio S¹, Terragna C¹, Ottaviani E¹, Grafone T¹
De Vivo A¹, Testoni N¹, Saglio G², Baccarani M^1
1Institute of Hematology and Medical Oncology “L. and A. Seràgnoli”, University of Bologna;
²Division of Hematology and Internal Medicine, Department of Clinical and Biological
Science, University of Turin; ³CEINGE Biotecnologie Avanzate and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II; ⁴Dipartimento di Medicina Clinica e Sperimentale, Sezione di
Ematologia, Università e Azienda Ospedaliera di Verona, Italy

The ubiquitin-proteasome system is an attractive target for anticancer drug development in several cancer including Chronic Myeloid Leukemia Ph⁺ (CML). The Bcr/Abl tyrosine kinase, the hallmark of CML, by multiple signaling/survival pathways downstream, including the ubiquitin-proteasome system, contributes to leukemic transformation Several key proteins that regulate important cellular processes such as proliferation and apoptosis are regulated by proteasome-dependent proteolysis. For these reasons, proteasome inhibitors represent a relatively new class of antineoplastic agents that act by interfering with the catalytic 20S core of the proteasome, thereby preventing the elimination of diverse cellular proteins targeted for degradation, including BCR-ABL. There are several classes of proteasome inhibitors including peptide aldehydes such as MG-132, the dipeptidyl boronic acid bortezomib, etc, with increased interest in the clinical development. Currently, the clinical utility of proteasome inhibitors in leukemia in general, and in CML in particular, remains relatively unexplored In this review we explore the molecular basis for use of this drugs in CML and the preliminary clinical utility of proteasome inhibitors in CML. [>Read full article in PDF]