慢性髓系白血病中 BCR/ABL 融合基因的患病率及树突状细胞的 T 细胞刺激能力

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.