Figure 2.

Treatment scenarios in acute myeloid leukemia (AML) and the impact of preleukemic hematopoietic stem cells (HSCs). (A) The ideal treatment would combine a therapy targeted against the frankly leukemic cells (such as anti-FLT3 therapy) to eradicate AML cells followed by a targeted therapy against the preleukemic cells (such as anti-DNMT3A therapy). This would lead to long-term durable remission and disease cure. (B) Current AML therapies largely target late mutations, such as FLT3-ITD, which are not present in preleukemic HSCs. In the event that all AML cells are eradicated, the preleukemic HSCs could eventually lead to relapsed disease. (C) Targeting of preleukemic HSCs in the context of high preleukemic burden could lead to bone marrow failure and cytopenias as the vast majority of HSCs would be targeted.