Mutation analysis of CD95 (APO-1/Fas) in childhood B-lineage acute lymphoblastic leukaemia.
The CD95 system plays an important role in lymphocyte homeostasis, has been implicated in the development of lymphoid malignancies, exerts a tumour suppressor function, and contributes to drug-induced cytotoxicity. We hypothesized that mutations of CD95 may occur in childhood B-lineage acute lymphoblastic leukaemia (ALL), a disease known for its constitutive resistance towards CD95-mediated apoptosis. We investigated 32 primary B-lineage ALL of childhood and five B-lineage ALL cell lines. All primary leukaemias expressed CD9 5 and bcl-2 to a variable degree. Most of the leukaemias were resistant towards CD95-mediated apoptosis. However, using SSCP analysis, no mutations in the coding and proximal promoter region could be detected. We conclude that the resistance towards CD95-mediated apoptosis observed in most de novo B-lineage ALL is not caused by mutations of the CD95 death receptor.
Universitäts-Kinderklinik Ulm, Germany.
C
C
Beltinger
T
T
Böhler
L
L
Karawajew
W D
WD
Ludwig
M
M
Schrappe
K M
KM
Debatin
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
D019014:fas Receptor