Assessing signaling pathways associated with in vitro resistance to cytotoxic agents in AML

Leuk Res. 2012 Jul;36(7):900-4. doi: 10.1016/j.leukres.2012.02.022. Epub 2012 Apr 21.

Abstract

This study uses single cell network profiling (SCNP) to characterize biological pathways associated with in vitro resistance or sensitivity to chemotherapeutics commonly used in acute myeloid leukemia (AML) (i.e. cytarabine/daunorubicin, gemtuzumab ozogamicin (GO), decitabine, azacitidine, clofarabine). Simultaneous measurements at the single cell level of changes in DNA damage, apoptosis and signaling pathway responses in AML blasts incubated in vitro with the above drugs showed distinct profiles for each sample and mechanistically different profiles between distinct classes of agents. Studies are ongoing to assess the clinical predictive value of these findings.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / pharmacology
  • Adolescent
  • Adult
  • Aged
  • Arabinonucleosides / pharmacology
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Child
  • Child, Preschool
  • Clofarabine
  • Cytotoxins / pharmacology*
  • Decitabine
  • Drug Resistance, Neoplasm* / genetics
  • Drug Resistance, Neoplasm* / physiology
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology*
  • Middle Aged
  • Models, Biological
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Tumor Cells, Cultured

Substances

  • Adenine Nucleotides
  • Arabinonucleosides
  • Cytotoxins
  • Clofarabine
  • Decitabine
  • Azacitidine