Leukemia and chromosomal instability in aged Fancc-/- mice

Exp Hematol. 2016 May;44(5):352-7. doi: 10.1016/j.exphem.2016.01.009. Epub 2016 Feb 6.

Abstract

Fanconi anemia (FA) is an inherited disorder of genomic instability associated with high risk of myelodysplasia and acute myeloid leukemia (AML). Young mice deficient in FA core complex genes do not naturally develop cancer, hampering preclinical studies on malignant hematopoiesis in FA. Here we describe that aging Fancc(-/-) mice are prone to genomically unstable AML and other hematologic neoplasms. We report that aneuploidy precedes malignant transformation during Fancc(-/-) hematopoiesis. Our observations reveal that Fancc(-/-) mice develop hematopoietic chromosomal instability followed by leukemia in an age-dependent manner, recapitulating the clinical phenotype of human FA and providing a proof of concept for future development of preclinical models of FA-associated leukemogenesis.

Publication types

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

MeSH terms

  • Acute Disease
  • Age Factors
  • Aging / genetics*
  • Aneuploidy
  • Animals
  • Chromosomal Instability*
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism
  • Fanconi Anemia Complementation Group C Protein / deficiency
  • Fanconi Anemia Complementation Group C Protein / genetics*
  • Hematopoiesis / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • Fancc protein, mouse
  • Fanconi Anemia Complementation Group C Protein