High frequency of rare structural chromosome abnormalities at relapse of cytogenetically normal acute myeloid leukemia with FLT3 internal tandem duplication

Theodore S. Gourdin, Ying Zou, Yi Ning, Ashkan Emadi, Vu H. Duong, Michael L. Tidwell, Ching Chen, Feyruz V. Rassool, Maria R. Baer*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

FLT3 internal tandem duplication (ITD) mutations are present in acute myeloid leukemia (AML) in 30% of patients with acute myeloid leukemia (AML),most commonly in those with a normal karyotype, and are associated with short relapse-free survival. Both invitro and invivo studies of FLT3-ITDcell lines have demonstrated reactive oxygen species-mediated DNA double-strand breaks and associated error-prone DNA repair as a mechanism of genomic instability, and we hypothesized that genomic instability might be manifested by cytogenetic changes at relapse of FLT3-ITD AML. We retrospectively reviewed charts of patients with cytogenetically normal (CN) FLT3-ITD AML treated at the University of Maryland Greenebaum Cancer Center, with attention to metaphase analysis results at relapse. Cytogenetic data were available from first and, when applicable, subsequent relapses for 15 patients diagnosed with CN FLT3-ITD AML. Among 12 patients with documented FLT3-ITD at first and, when applicable, subsequent relapse, 10 had cytogenetic changes, including nine with rare structural abnormalities. The high frequency of rare structural chromosome abnormalities at relapse in our case series supports a role of genomic instability in the genesis of relapse, and suggests that reactive oxygen species-generating and DNA repair pathways might be therapeutic targets in FLT3-ITD AML.

Original languageEnglish (US)
Pages (from-to)467-473
Number of pages7
JournalCancer Genetics
Volume207
Issue number10-12
DOIs
StatePublished - Oct 1 2014

Keywords

  • Acute myeloid leukemia
  • Cytogenetics
  • FLT3-ITD
  • Genomic instability
  • Relapse

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'High frequency of rare structural chromosome abnormalities at relapse of cytogenetically normal acute myeloid leukemia with FLT3 internal tandem duplication'. Together they form a unique fingerprint.

  • Cite this