Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells

Yan Xie, Johan P. De Winter, Quinten Waisfisz, Aggie W.M. Nieuwint, Rik J. Scheper, Fré Arwert, Maureen E. Hoatlin, Gert Jan Ossenkoppele, Gerrit Jan Schuurhuis, Hans Joenje

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Fanconi anaemia (FA) is an autosomal recessive disease strongly predisposing to bone marrow failure and acute myeloid leukaemia (AML). Four FA genes, corresponding to complementation groups A, C, F and G, have been cloned, but the molecular functions of the corresponding proteins are unknown. The high risk of AML in FA patients suggests that the "FA pathway" helps to prevent AML in non-FA individuals. We examined 10 AML cell lines, as well as primary cells from 15 AML patients representing the French-American-British subclasses M1 - M5a, for possible deficiencies in the "FA pathway". Cellular lysates were analysed for the presence of the FA proteins FANCA, FANCC, FANCF and FANCG, as well as the complexes reported to be formed between these proteins, using immunoprecipitation and Western blot analysis. Aberrant protein profiles were observed in five of the 10 cell lines and in 11 of the 15 primary AML samples. Aberrations, that included absence or reduced presence of FA proteins and/or their complexes, were noted in the subclasses M1 - M4, but not in M5a (n = 3). Our results suggest that a significant proportion of general AML is characterized by a disturbance of the "FA pathway" that may represent an early event in the development of this type of leukaemia.

Original languageEnglish (US)
Pages (from-to)1057-1064
Number of pages8
JournalBritish Journal of Haematology
Volume111
Issue number4
DOIs
StatePublished - Dec 1 2000

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Keywords

  • Acute myeloid leukaemia
  • Cancer predisposition
  • Caretaker genes
  • Fanconi anaemia
  • Tumour suppression

ASJC Scopus subject areas

  • Hematology

Cite this

Xie, Y., De Winter, J. P., Waisfisz, Q., Nieuwint, A. W. M., Scheper, R. J., Arwert, F., Hoatlin, M. E., Ossenkoppele, G. J., Schuurhuis, G. J., & Joenje, H. (2000). Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells. British Journal of Haematology, 111(4), 1057-1064. https://doi.org/10.1046/j.1365-2141.2000.02450.x