Clinical significance of in vivo cytarabine-induced gene expression signature in AML

Leuk Lymphoma. 2016;57(4):909-20. doi: 10.3109/10428194.2015.1086918. Epub 2015 Oct 16.

Abstract

Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

Keywords: Cytarabine; acute myeloid leukemia; event-free survival; gene expression.

Publication types

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

MeSH terms

  • Adolescent
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Child
  • Child, Preschool
  • Cytarabine / pharmacology*
  • Cytarabine / therapeutic use
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic / drug effects*
  • Gene Knockdown Techniques
  • Gene Regulatory Networks
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Reproducibility of Results
  • Transcriptome*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • RNA, Small Interfering
  • Cytarabine