Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models

Fernando F. Corrales-Medina; Christa A. Manton; Robert Z. Orlowski; Joya Chandra

doi:10.1016/j.leukres.2014.12.014

Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models

Fernando F. Corrales-Medina, Christa A. Manton, Robert Z. Orlowski, Joya Chandra

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.

Original language	English (US)
Pages (from-to)	371-379
Number of pages	9
Journal	Leukemia Research
Volume	39
Issue number	3
DOIs	https://doi.org/10.1016/j.leukres.2014.12.014
State	Published - Mar 1 2015

Keywords

Acute myeloid leukemia
Bortezomib
Marizomib
Multiple myeloma
Panobinostat

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1016/j.leukres.2014.12.014

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title = "Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models",

abstract = "Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.",

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AU - Corrales-Medina, Fernando F.

AU - Manton, Christa A.

AU - Orlowski, Robert Z.

AU - Chandra, Joya

PY - 2015/3/1

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AB - Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.

KW - Acute myeloid leukemia

KW - Bortezomib

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Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models

Abstract

Keywords

ASJC Scopus subject areas

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