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Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.


ABSTRACT: In this work, effects of bortezomib on apoptosis, clonal progenitor growth, cytokine production, and NF-?B 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-?B 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.

SUBMITTER: Liesveld JL 

PROVIDER: S-EPMC4557209 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.

Liesveld Jane L JL   Rosell Karen E KE   Bechelli Jeremy J   Lu Chaohui C   Messina Patti P   Mulford Deborah D   Ifthikharuddin J J JJ   Jordan Craig T CT   Phillips Ii Gordon L GL  

Cancer investigation 20110801 7


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 chemo  ...[more]

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