Article

Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines

Department of Medicine, Hematology/Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA. jane
Cancer Investigation (Impact Factor: 2.06). 08/2011; 29(7):439-50. DOI: 10.3109/07357907.2011.590567
Source: PubMed

ABSTRACT In this work, effects of bortezomib on apoptosis, clonal progenitor growth, cytokine production, and NF-κB expression in patients with MDS with cytopenias requiring transfusion support are examined. Bortezomib increased apoptosis in marrow mononuclear cells but had no effects on CFU-GM, BFU-E, or CFU-L content. No consistent effects on NF-κB activation in vivo were noted. To further define the role of bortezomib in AML and MDS, we examined it in combination with several targeted agents and chemotherapeutic agents in vitro. Combinations with arsenic trioxide, sorafenib, and cytarabine demonstrated synergistic in vitro effects in AML cell lines.

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    • "The ORR was 56%, with 14 achieving hematologic improvement [83]. Bortezomib is a proteasome and NF-kb inhibitor that can induce apoptosis in vitro in MDS/AML leukemia bone marrow cells [84] and has demonstrated benefit when used as a single agent in MDS patients [85]. Bortezomib has been studied in combination with lenalidomide, low-dose cytarabine (LDAC) and the HDACi Belinostat in patients with AML and higher-risk MDS, though its benefit remains unclear [86e88]. "
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