Dendritic cell (DC) vaccines are promising for immunotherapy, and their production using CD34+ hematopoietic stem cells (HPSCs) from patients with chronic myelogenous leukemia (CML) and healthy donors is well established. However, the generation of CD1a+CD14- DCs and their functional properties in patients with CML remain elusive. Here, we aimed to study the biology of DCs generated from CD34-/low HPSCs and evaluate the status of their BCR/ABL translocation, ability to stimulate T cells, and capacity of endocytosis compared to DCs derived from CD34+ HPSCs from both patients with CML and healthy donors. CD1a+CD14- DCs were generated from CD34-/low HPSCs and evaluated morphologically and functionally. CD34+ cells are frequently selected for transplantation and the entire CD34-/low HPSC fraction is wasted. Here, we anticipated the CD34- HPSC subset to constitute an invaluable source for acquiring DCs for immunotherapy. CD34+ and CD34- HPSCs were sorted from the bone marrow samples of CML patients and healthy donors and differentiated ex vivo in a similar way. DCs from CD34-Lin- and CD34+Lin- HPSCs expressed comparable surface markers (CD80, CD83, CD86, HLA-DR, CD40, and CD54). Functional analysis revealed that DCs acquired from both subsets retained a potent allogeneic T cell stimulatory capacity and an efficient phagocytic ability and showed a similar BCR/ABL translocation status. In conclusion, DCs were successfully differentiated from the CD34-Lin- cell subset and showed potent functional capacities, indicating their potential for application in immunotherapy and basic research.
Keywords: CD34+; CD34-Lin-; chronic myelogenous leukemia; dendritic cells; hematopoietic stem cell; immunotherapy.
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