Abstract
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.
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Acknowledgements
We are indebted to our patients and healthy blood donors, their parents and physicians for the commitment to this study. We thank A Frank-Hoppe for excellent study support. This work was supported by a grant of the Kind-Philipp-Stiftung für Leukämieforschung (BM, DM) and Hannover Medical School (HiLF).
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Maecker, B., Mougiakakos, D., Zimmermann, M. et al. Dendritic cell deficiencies in pediatric acute lymphoblastic leukemia patients. Leukemia 20, 645–649 (2006). https://doi.org/10.1038/sj.leu.2404146
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DOI: https://doi.org/10.1038/sj.leu.2404146
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