Hypothesis: myeloid-restricted hematopoietic stem cells with self-renewal capacity may be the transformation site in acute myeloid leukemia.

The transformation site in acute myeloid leukemia (AML) has been proposed to be pluripotent hematopoietic stem cells (PHSCs), and the lymphoid development of leukemic PHSCs may be suppressed by leukemogenic events. Recent data from multiple laboratories have contradicted the current hierarchical model of hematopoiesis and indicated the presence of myeloid HSCs with minimal lymphopoietic potential (MyHSCs) in mice. Based on these findings and re-evaluating the published data on AML stem cells, we hypothesize that MyHSCs may be the transformation site in AML. If so, therapy targeting leukemic MyHSCs but sparing PHSCs is worth investigating.