Skip to main content
 

Mechanistic heterogeneity in refractory AML

Wednesday, September 12, 2018 — Poster Session II

3:30 p.m. – 5:00 p.m.
FAES Terrace
NCI
CANCER-16

Authors

  • S Horibata
  • J Lack
  • CB DeStefano
  • MM Gottesman
  • CS Hourigan

Abstract

Successful clinical remission after induction therapy for acute myeloid leukemia (AML) is required for long-term survival to be achieved. Despite trends in improved survival due to better supportive care, up to 40% of patients will have primary refractory disease which has a poorly understood biology and carries a dismal prognosis. The development of effective treatment strategies has been hindered by a general lack of knowledge on mechanisms of chemotherapy resistance. Here, through transcriptomic analysis of 150 cases of treatment naïve AML, three resistant subpopulations with distinct expression profiles are identified. These subpopulations have differential activity in pathways involved in cell cycle, transcription, translation, metabolism, and/or stem-cell properties. Ex-vivo drug sensitivity to 122 small molecule inhibitors revealed effective group-specific targeting of pathways among these three refractory groups. Proper characterization and tailored treatment for refractory AML could improve patient outcomes and should be studied prospectively in clinical trials.

Category: Cancer Biology