CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia

Autor: Beltinger C, Kurz E, Böhler T, Schrappe M, Wd, Ludwig, Klaus-Michael Debatin
Rok vydání: 1998
Předmět:
Male
Heterozygote
Adolescent
Immunology
DNA Mutational Analysis
chemical and pharmacologic phenomena
Apoptosis
Biochemistry
Polymerase Chain Reaction
Fatal Outcome
Adrenal Cortex Hormones
Recurrence
hemic and lymphatic diseases
Consensus Sequence
Tumor Cells
Cultured
Humans
Leukemia-Lymphoma
Adult T-Cell
fas Receptor
Child
Promoter Regions
Genetic
Polymorphism
Single-Stranded Conformational
Binding Sites
Gene Expression Regulation
Leukemic
Infant
hemic and immune systems
Cell Biology
Hematology
DNA
Neoplasm
Exons
Precursor Cell Lymphoblastic Leukemia-Lymphoma
biological factors
Neoplasm Proteins
DNA-Binding Proteins
Transcription Factor AP-2
Drug Resistance
Neoplasm
Child
Preschool
Female
biological phenomena
cell phenomena
and immunity
Polymorphism
Restriction Fragment Length
Transcription Factors
Zdroj: Europe PubMed Central
ISSN: 0006-4971
Popis: CD95 (APO-1/Fas)-mediated apoptosis is pivotal in normal lymphocyte homeostasis and mutations of CD95 cause a benign autoimmune lymphoproliferation syndrome (ALPS) in humans and mice. However, tumors only rarely develop in these patients, and no CD95 mutations have yet been directly implicated in tumorigenesis. We therefore examined 81 de novo childhood T-lineage acute lymphoblastic leukemias (T-ALL) including 54 steroid-poor responders, 10 relapsed T-ALL, and 10 leukemic T-cell lines, for the presence of CD95 mutations using single-strand confirmation polymorphism and sequence analysis. In leukemic blasts and normal T cells of one patient, a heterozygous mutation in exon 3 of CD95 causing a 68Pro → 68Leu change associated with decreased CD95-mediated apoptosis was found. In leukemic blasts and normal T cells of a second patient, a homozygous mutation in the promoter of CD95 causing disruption of a consensus sequence for AP-2 binding without decreasing constitutive CD95 expression was detected. No large intragenic alterations of CD95 were found, no homozygous loss was detected in the cell lines, and no CD95 mutations were detected in the relapses. The data presented here show that CD95 mutations occur in some T-ALL and may be of biological importance.
Databáze: OpenAIRE
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