Expression of CD27-CD70 on early B cell progenitors in the bone marrow: implication for diagnosis and therapy of childhood ALL.
OBJECTIVE
CD27, a member of the TNF receptor family, plays an important role in lymphoid proliferation, differentiation and apoptosis. This study addresses the expression of CD27 and its ligand, CD70, in children with acute lymphoblastic leukemia (ALL) and the possible role of this receptor-ligand pair in the pathogenesis of ALL.


METHODS
Expression of CD27 and CD70 was evaluated with three-color flow cytometry in blood and bone marrow (BM) samples in children with ALL and controls. The biological role of these molecules on leukemic cell proliferation was studied in an in vitro culture system.


RESULTS
The expression of the membrane bound CD27, as well as membrane bound CD70, on CD19(+) cells in the BM was significantly increased in ALL children compared to the expression found in the controls. Importantly, a substantial reduction in the in vitro proliferation of leukemic cells could be observed when the leukemic cells were cultured in presence of a blocking anti-human CD70 monoclonal antibody. The level of soluble CD27 (sCD27) in serum was also investigated and found to be significantly elevated in leukemic children as compared to healthy children.


CONCLUSIONS
The high expression of CD27 and CD70 on ALL cells may represent an amplification of the normal CD27-CD70 expression present on early B cell progenitors. Our finding suggests that interference with CD27-CD70 interaction may represent novel treatment opportunities in ALL. Further studies are required to pin-point the role of this receptor-ligand pair in normal and malignant hematopoiesis.
Nilsson
Anna
A
Pediatric Cancer Research Unit, Astrid Lindgren Children Hospital, Stockholm, Sweden. Anna.Nilsson@mtc.ki.se
de Milito
Angelo
A
Mowafi
Frida
F
Winberg
Gösta
G
Björk
Olle
O
Wolpert
Elisabeth Z
EZ
Chiodi
Francesca
F
D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D053282:CD27 Ligand; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008565:Membrane Proteins / Q000032:analysis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis*; D048069:Tumor Necrosis Factors / Q000032:analysis*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D053282:CD27 Ligand; C505771:CD70 protein, human; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors