Death induction by CD99 ligation in TEL/AML1-positive acute lymphoblastic leukemia and normal B cell precursors.
Our study was performed to examine the role of CD99 in normal and leukemia BCPs. CD99 is strongly expressed by certain pediatric cancers including BCP-ALL. Modulation of the antigen in ETs and T cells induces apoptosis, hence implicating CD99 as a potential target for anti-cancer therapy. However, nothing is known about these aspects in BCPs. We investigated BCP-ALL cases and normal BCP cells from pediatric BM for CD99 protein and RNA expression as well as for effects of CD99 modulation by mAb. Immunophenotypes, recovery, apoptosis, and aggregation were assessed. Flow cytometry, light microscopy, and qRT-PCR were used in our experiments. An association of CD99 expression levels with the cytogenetic background of pediatric BCP-ALLs was found. Highest CD99 levels were observed in hyperdiploid, followed by TEL/AML1 and random karyotype leukemias. CD99 ligation moderately induced cell death only in TEL/AML1 cases. Stroma cell contact mitigated this effect. Very immature normal BCPs were the most sensitive to CD99-mediated death induction. Type I CD99 mRNA was the main isoform in ALLs and was expressed differentially during BCP maturation. Our data suggest that clinical targeting of CD99 may be effective in BCP-ALL-bearing TEL/AML1 but also may elicit negative effects on normal B-lymphopoiesis. We consider our results as an indication that CD99 may play a physiologic role in the clonal deletion processes necessary for B-lymphoid selection.
Husak
Zvenyslava
Z
St. Anna Kinderkrebsforschung, Children's Cancer Research Institute, Zimmermannplatz 10, A-1090 Vienna, Austria.
Printz
Dieter
D
Schumich
Angela
A
Pötschger
Ulrike
U
Dworzak
Michael N
MN
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016923:Cell Death; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit; D006801:Humans; D038041:Lymphopoiesis; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D000097764:ETS Translocation Variant 6 Protein
D000071443:12E7 Antigen; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C061828:CD99 protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein