acute lymphoblastic leukemia

Dendritic cell deficiencies in pediatric acute lymphoblastic leukemia patients

Maecker B, Mougiakakos D, Zimmermann M, Behrens M, Hollander S, Schrauder A, Schrappe M, Welte K, Klein C.
Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.

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.

Leukemia. 2006 Feb 23