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CD95 (APO-1/Fas) Mutations in Childhood T-Lineage Acute
Lymphoblastic Leukemia
Christian Beltinger,
Elke Kurz,
Thomas Böhler,
Martin Schrappe,
Wolf-Dieter Ludwig, and
Klaus-Michael Debatin
From the Sektion Hämatologie/Onkologie,
Universitäts-Kinderklinik and Abteilung Molekulare Onkologie,
Deutsches Krebsforschungszentrum (German Cancer Research Center),
Heidelberg, Germany; the Abteilung Pädiatrische Hämatologie
und Onkologie, Medizinische Hochschule Hannover, Germany; and the
Abteilung für Hämatologie, Onkologie, und Tumorimmunologie,
Robert-Rössle-Klinik, Humboldt Universität Berlin, Germany.
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.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3943-3951
© 1998 by The American Society of Hematology.
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