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

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


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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminoglycosides / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Gemtuzumab
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Myeloid Cell Leukemia Sequence 1 Protein / physiology*
  • Peptide Fragments / physiology
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology
  • Vorinostat


  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Bax protein (53-86)
  • Hydroxamic Acids
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • PMAIP1 protein, human
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Vorinostat
  • Gemtuzumab