Fig. 1.

CD34⁺CD38⁻ phenotype functionally defines primary human AML LSCs and human normal HSCs in vivo. (A to C) Xenotransplantation of CD34⁺CD38⁻ primary human AML cells results in initiation of AML. pDC, plasmacytoid DC; cDC, conventional DC. In AML-engrafted recipients, (A) BM is entirely replaced with hCD45⁺CD33⁺ cells with the complete absence of the normal immune subsets such as DCs, T cells and B cells and (B) PB hCD45⁺CD33⁺ cells show uniform-appearing blast-like morphology by May-Grunwald-Giemsa staining. (C) BM of recipients of CD34⁺CD38⁻ AML cells was reconstituted with CD34⁺CD38⁻, CD34⁺CD38⁺, and CD34⁻ cells. Serial transplantation of CD34⁺CD38⁻ cells results in complete replacement of the secondary recipient BM with hCD45⁺CD33⁺ cells. (D to F) Normal human CB CD34⁺CD38⁻ cells are HSCs capable of long-term multilineage reconstitution of human hematopoiesis. In recipients of normal CB CD34⁺CD38⁻ cells, (D) BM contains heterogeneous human hematopoietic cell types, including T cells, B cells, and DC subsets, by phenotype and (E) PB hCD45⁺CD33⁺ cells contain morphologically heterogeneous hematopoietic cells. (F) Transplantation of normal human CB CD34⁺CD38⁻ cells results in the reconstitution of recipient BM with CD34⁺CD38⁻, CD34⁺CD38⁺, and CD34⁻ cells (left). BM of secondary CD34⁺CD38⁻ cell recipient contains both hCD33⁺CD45⁺ human myeloid and hCD33⁻ CD45⁺ human lymphoid cells (right).