Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells.

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.

journal_name

Br J Haematol

authors

Xie Y,de Winter JP,Waisfisz Q,Nieuwint AW,Scheper RJ,Arwert F,Hoatlin ME,Ossenkoppele GJ,Schuurhuis GJ,Joenje H

subject

Has Abstract

pub_date

2000-12-01 00:00:00

pages

1057-64

issue

4

eissn

0007-1048

issn

1365-2141

pii

bjh2450

journal_volume

111

pub_type

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