Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells

Fanconi anaemia (FR) is an autosomal recessive disease strongly predisposin g to bone marrow failure and acute myeloid leukaemia (AML). Four FA genes, corresponding to complementation groups A, C, F and G, have been cloned, bu t the molecular functions of the corresponding proteins are unknown, The hi gh risk of AML in FA patients suggests that the 'FA pathway' helps to preve nt AML in non-FA individuals, We examined 10 AML tell lines, as well as pri mary cells from 15 AML patients representing the French-American-British su bclasses M1-M5a, for possible deficiencies in the 'FA pathway', Cellular ly sates were analysed for the presence of the FA proteins FANCA, FANCC, FANCF and FANCC, as well as the complexes reported to be formed between these pr oteins, using immunoprecipitation and Western blot analysis. Aberrant prote in 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 m ay represent an early event in the development of this type of leukaemia.