Involvement of Fanconi anemia genes FANCD2 and FANCF in the molecular basis of drug resistance in leukemia

Mol Med Rep. 2015 Jun;11(6):4605-10. doi: 10.3892/mmr.2015.3288. Epub 2015 Jan 30.

Abstract

The Fanconi anemia (FA)‑associated proteins FANCF and FANCD2 are important components of the FA pathway of DNA crosslink repair. FANCF and FANCD2 have been found to be involved in drug‑resistant multiple myeloma, ovarian cancer, non‑small‑cell lung cancer, and head and neck cancer. However, it is unclear whether these two genes participate in adriamycin (ADR)‑resistant leukemia. Therefore, the aim of the current study was to investigate FANCF and FANCD2 expression in drug‑resistant and drug‑sensitive leukemia cells. Western blot analysis revealed enhanced FANCF expression and monoubiquitination of FANCD2 in ADR‑resistant cells. Additionally, it was observed that drug‑resistant cells had reduced DNA damage compared with drug‑sensitive cells. The results of this study indicate that the FA pathway may confer leukemia resistance to ADR via enhanced DNA interstrand crosslink repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Damage / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Fanconi Anemia Complementation Group D2 Protein / genetics*
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Fanconi Anemia Complementation Group F Protein / genetics*
  • Fanconi Anemia Complementation Group F Protein / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • K562 Cells
  • Leukemia / metabolism
  • Leukemia / pathology
  • S Phase Cell Cycle Checkpoints / drug effects
  • Signal Transduction / drug effects
  • Ubiquitination / drug effects

Substances

  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group F Protein
  • Doxorubicin