Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells.
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.
Xie
Y
Y
Department of Clinical Genetics and Human Genetics, Free University Medical Centre, Amsterdam, The Netherlands.
de Winter
J P
JP
Waisfisz
Q
Q
Nieuwint
A W
AW
Scheper
R J
RJ
Arwert
F
F
Hoatlin
M E
ME
Ossenkoppele
G J
GJ
Schuurhuis
G J
GJ
Joenje
H
H
D000208:Acute Disease; D000328:Adult; D015153:Blotting, Western / Q000379:methods; D001854:Bone Marrow Cells / Q000378:metabolism; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000032:analysis*; D005199:Fanconi Anemia / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D052219:Fanconi Anemia Complementation Group F Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011233:Precipitin Tests / Q000379:methods; D011506:Proteins / Q000032:analysis*; D016601:RNA-Binding Proteins / Q000032:analysis*; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; C497651:FANCC protein, human; C499901:FANCF protein, human; C499909:FANCG protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D052219:Fanconi Anemia Complementation Group F Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins