Targeting LIC–stroma interaction in combination with FLT3-TKI. (A) Treatment of leukemic blasts with chemotherapy (CT) or FLT3-TKIs kills cycling cells in PB and BM whereas LICs and HSCs are embedded in their niche and protected against apoptotic cell death. (B) Targeting LIC–stroma cell interaction using neutralizing antibodies or small peptides disrupts stroma-mediated survival signals and releases LIC but also HSCs from their environment. (C) As a consequence, FLT3-ITD–expressing LICs enter the cell cycle and become sensitive to FLT3-TKIs, while normal HSCs are spared. (D) Finally, HSCs adhere to stromal cells again and initiate hematopoietic reconstitution.