Dendritic cell deficiencies in pediatric acute lymphoblastic leukemia patients.
Acute lymphoblastic leukemia (ALL) cells are particularly poor at generating anti-leukemia immunity, despite residing in lymphoid organs. To assess a potential role of dendritic cells (DC) in poor anti-leukemia immunity, we analyzed peripheral blood DC in 55 pediatric ALL patients at the time of initial diagnosis and 19 age-matched healthy controls. Dendritic cells were identified by their expression of HLA-DR, lack of B, T, NK, and monocyte markers, and expression of CD11c (myeloid DC(mDC)) or BDCA-2 (plasmacytoid DC(pDC)) using flow cytometry. We found that in children with B-lineage ALL, numbers of both mDC and pDC were significantly reduced (P = 0.0001). In contrast, T-lineage ALL patients showed normal pDC and significantly elevated mDC (P = 0.003) levels, with normal expression of HLA-DR and co-stimulatory molecules. A decrease in DC could not be explained by general impairment of myelopoiesis, as we could not demonstrate a correlation of DC numbers with granulocyte/monocyte numbers in patients with B-lineage ALL. However, aberrant expression of myeloid surface markers on leukemic blasts was frequent in patients lacking myeloid DC indicating a potential block of DC differentiation. Thus, depletion of DC in B-lineage ALL patients may contribute to poor anti-leukemia immune responses.
Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany. maecker.britta@mh-hannover.de
B
B
Maecker
D
D
Mougiakakos
M
M
Zimmermann
M
M
Behrens
S
S
Hollander
A
A
Schrauder
M
M
Schrappe
K
K
Welte
C
C
Klein
D000293:Adolescent; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D039521:CD11c Antigen / Q000096:biosynthesis*; D018826:CD13 Antigens / Q000096:biosynthesis; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000096:biosynthesis*; D007958:Leukocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000096:biosynthesis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D012680:Sensitivity and Specificity; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; C571163:CD33 protein, human; C443299:CLEC4C protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D063268:Sialic Acid Binding Ig-like Lectin 3; D009195:Peroxidase; D018826:CD13 Antigens