The BCAA-free diet suppresses human acute leukemia development in xenotransplantation models. (A) The schema for xenogeneic transplantation experiments to evaluate the effects of a BCAA-free diet on leukemia progression. (B) Changes in the concentration of serum BCAA in NSG mice 2 weeks after commencement of the BCAA-free diet. (C) Sequential changes in percentages of human cell chimerism in the blood of NSG mice reconstituted with normal CD34⁺ HSPCs after starting the BCAA-free diet (blue line, control group and red line, BCAA-free group). (D) Human cell chimerism in the bone marrow of NSG mice reconstituted with normal CD34⁺ HSPCs at 7 weeks after starting the BCAA-free diet. (E) Frequencies of hCD45⁺ hCD34⁺ HSPCs in the bone marrow of the NSG mice reconstituted with normal CD34⁺ HSPCs are shown. (F) Evaluation of engraftment and reconstitution potential of human AML and ALL cells in NSG mice fed the BCAA-free or control diet. Recipient mice were fed either diet, 10 days before transplantation. Six to 8 weeks after transplantation, tumor burdens were evaluated in the bone marrow. Results from 4 independent experiments are shown. (G) Percentages of human acute leukemia cells in the bone marrow of each group. (H) The changes in the frequency of CD34⁺ immature AML fraction during dietary restriction of BCAA in vivo. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, panels B, C, and H, mean ± SEM. BM, bone marrow; PB, peripheral blood; Ph, Philadelphia chromosome.