title: Assessing signaling pathways associated with in vitro resistance to cytotoxic agents in AML.
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.
authors.affiliation: Department of Research, Nodality Inc, South San Francisco, CA, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Rosen
authors.forename: James A
authors.initials: JA
authors.lastname: Cordeiro
authors.forename: Aileen
authors.initials: A
authors.lastname: Cohen
authors.forename: Norman
authors.initials: N
authors.lastname: Lacayo
authors.forename: Donna
authors.initials: D
authors.lastname: Hogge
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Hawtin
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cesano
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001087:Arabinonucleosides / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D003603:Cytotoxins / Q000494:pharmacology*; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003603:Cytotoxins; D000077866:Clofarabine; D000077209:Decitabine; D001374:Azacitidine