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Leuk Res. 2014 May;38(5):564-8. doi: 10.1016/j.leukres.2014.02.007. Epub 2014 Feb 28.

Mcl-1 dependence predicts response to vorinostat and gemtuzumab ozogamicin in acute myeloid leukemia.

Author information

1
Eutropics Pharmaceuticals, Inc., Cambridge, MA, United States. Electronic address: wpierceall@eutropics.com.
2
Eutropics Pharmaceuticals, Inc., Cambridge, MA, United States.
3
Stanford University, Stanford, CA, United States.
4
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States. Electronic address: rwalter@fhcrc.org.

Abstract

Older adults with acute myeloid leukemia (AML) are commonly considered for investigational therapies, which often only benefit subsets of patients. In this study, we assessed whether BH3 profiling of apoptotic functionality could predict outcomes following treatment with vorinostat (histone deacetylase inhibitor) and gemtuzumab ozogamicin (GO; CD33-targeted immunoconjugate). Flow cytometry of BH3 peptide priming with Noxa (anti-apoptotic protein Mcl-1 modulator) correlated with remission induction (p=.026; AUC=0.83 [CI: 0.65-1.00; p=.00042]: AUC=0.88 [CI:0.75-1.00] with age adjustment) and overall survival (p=.027 logistic regression; AUC=0.87 [0.64-1.00; p=.0017]). This Mcl-1-dependence suggests a pivotal role of Bcl-2 family protein-mediated apoptosis to vorinostat/GO in AML patients.

KEYWORDS:

AML; Biomarker; Gemtuzumab ozogamicin; HDAC inhibitors; Personalized medicine

PMID:
24636337
PMCID:
PMC4104771
DOI:
10.1016/j.leukres.2014.02.007
[Indexed for MEDLINE]
Free PMC Article

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