Extended Data Fig. 4: Dietary valine deprivation/restriction reduce leukemic burden and increases survival in mice.
From: Valine tRNA levels and availability regulate complex I assembly in leukaemia
a, Kaplan-Meier curve representing morbidity of recipient mice transplanted with ckit+ cells transduced with either pMIG (n=8) or NOTCH1-ΔE-IRES-GFP (n=9) (Log-rank test, two-sided). b, Representative image of spleen from mice secondary transplanted with NOTCH-ΔE-GFP+ tumors and fed either control diet or valine-deficient diet for 3 weeks. c, Absolute leukemic burden in peripheral blood from mice fed either control diet or valine deficient diet for 3 weeks (mean ± SD of n=5 animals; two-sided unpaired t-test). d, Percentage annexin V positive cells (mean ± SD of n=3 animals; two-sided unpaired t-test). e, Absolute leukemic burden in peripheral blood from the mice transplanted with NOTCH-ΔE-GFP+ tumors and fed complete amino acid diet (n=7) or diets deficient in either valine (n=7), lysine (n=6) or asparagine (n=6); (mean ± SD of individual animals; two-sided unpaired t-test). f, Kaplan–Meier survival graph of mice represented in (e) (Log-rank test, two-sided). g, Representative image of spleen from mice fed different diets in (e) and (f). h, Peripheral tumor burden in mice fed valine deficient diet for 2 weeks at late stages of tumor development (n=10; two-sided unpaired t-test). i, Percentage GFP+ cells in peripheral blood of mice transplanted with (BCR-ABL-GFP+) tumors and fed either control diet or valine-deficient diet for 2 weeks (mean ± SD of n = 4 animals; two-sided unpaired t-test). j, Kaplan–Meier survival graph of NSG mice transplanted with patient derived xenograft T-ALL PDX_1 and fed either control diet (n=5) or valine deficient diet (n=5) (Log-rank test, two-sided). Death owing to leukemia or toxicity of valine deprivation is highlighted. k, Body weights of NSG mice transplanted with T-ALL PDX_1 and fed either control valine proficient diet or valine deficient diet (mean ± SD of n=5 animals; two-sided unpaired t-test). l, Schematic representation of secondary transplant experiment to test sensitivity of T-ALL to decreasing levels of dietary valine (created with Biorender.com). m, Body weights of C57BL/6 mice secondary transplanted with NOTCH-ΔE GFP+ tumors and fed either control valine proficient diet (n=5) or valine deficient diet (n=5) or valine deficient diet substituted with 0.8g/l valine (n=4) or 0.4g/l in drinking water (n=5) (mean ± SD of individual animals; two-sided unpaired t-test).
