Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines
Jane L Liesveld, Karen E Rosell, Jeremy Bechelli, Chaohui Lu, Patti Messina, Deborah Mulford, J J Ifthikharuddin, Craig T Jordan, Gordon L Phillips Ii, Jane L Liesveld, Karen E Rosell, Jeremy Bechelli, Chaohui Lu, Patti Messina, Deborah Mulford, J J Ifthikharuddin, Craig T Jordan, Gordon L Phillips Ii
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.
Trial registration: ClinicalTrials.gov NCT00262873.
Conflict of interest statement
DECLARATION OF INTEREST
The authors report no conflicts of interest.
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Source: PubMed