ELDR overexpression inhibits growth of AML in xenografts. (A) s.c. xenografts of ELDR-overexpressing THP-1 cell lines (ELDR-C1, ELDR-C3) and the EV control cell lines (EV1, EV2) in NSG mice. (B) Volume of tumors over time after the xenograft for ELDR-overexpressing line (ELDR-C1) and the EV1 control line measured by caliper. n = 6 mice in each group. (C) Weight of tumors at 4 weeks after the xenograft for ELDR-C1 and the EV1 control line. n = 6 mice in each group. (D) IV xenografts of ELDR-overexpressing THP-1 cell lines (ELDR-C1 and ELDR-C3) or EV1 control lines or NT THP-1 cells NT in NSG mice. (E) Percent of human CD45+ cells measured by FACS in organs of animals transplanted with the ELDR-C1 line or the EV1 control line 4 weeks after the IV xenograft. (F) Kaplan-Meier curve revealing disease-free survival after IV xenograft of the THP-1 ELDR-overexpressing cell lines ELDR-C1 and ELDR-C3 or the EV1 control line or NT cells as controls in NSG mice. n = 7 mice (ELDR-C1, ELDR-C3), n = 5 mice (EV1), n = 3 mice (NT); (statistical analysis: ELDR-C1 or ELDR-C3 vs EV1 or NT). (G) IV xenografts of the ELDR-overexpressing Mono-Mac-1 cell line (ELDR-C5, ELDR-C7) or the EV2 control line or NT Mono-Mac-1 cells (NT) in NSG mice. (H) Spleen weight of mice at 4 weeks after the xenograft that received ELDR-overexpressing Mono-Mac-1 cell lines ELDR-C5 and ELDR-C7 or the EV control cell line (EV2) or NT Mono-Mac-1 cells. n = 3 mice (EV2, ELDR-C5, ELDR-C7); n = 2 mice (NT). (I) Kaplan-Meier curve revealing disease-free survival of mice after an IV xenograft of the Mono-Mac-1 ELDR-overexpressing cell line ELDR-C5 or the EV2 and NT as controls in NSG mice. n = 6 mice (ELDR-C5), n = 3 mice (EV2), n = 3 mice (NT); (statistical analysis: ELDR-C5 vs EV2 or NT). (J) IV xenograft of ELDR-overexpressing cell line (ELDR-C1-Luc) or EV control line (EV-Luc) that also expresses a luciferase reporter gene into NSG mice. (K) Visualization of leukemic cells through monitoring of the luciferase signal. The figure illustrated is representative of the image captured on day 10 after IV injection and (L) quantification of radiance after the xenograft for the line ELDR-C1-Luc and the EV-Luc control line. n = 5 mice per group. (M) Kaplan-Meier curve revealing disease-free survival after IV xenograft of the THP-1 ELDR-overexpressing cell line ELDR-C1-Luc or the EV-Luc control line in NSG mice. n = 5 mice per group. (N) Visualization of leukemic cells (ELDR-C1-Luc) through monitoring of the luciferase signal after treatment of animals with LSD1i (GSK2879552)/ATRA or vehicle. The figure is representative of the image captured on day 18 of the treatment. (O) Quantification of radiance in mice after the xenograft of the line ELDR-C1-Luc and treatment of animals with LSD1i/ATRA or vehicle. n = 10 mice per group. (P) IV xenograft of ELDR-overexpressing THP-1 cell line (ELDR-C1ctrl) or the EV control cell line (EV1ctrl) vs ELDR-deleted cell line ELDR-C1del ELDR. (del ELDR: CRISPR/Cas9 with gRNAs specific to ELDR; ctrl: CRISPR/Cas9 with nontargeting gRNAs) into NSG mice. (Q) Kaplan-Meier curve for disease-free survival of mice after an IV xenograft of the ELDR-overexpressing cell line ELDR-C1ctrl vs the EV1ctrl and ELDR-C1delELDR as controls in NSG mice. n = 3 mice per group; (statistical analysis: ELDR-C1ctrl vs EV1ctrl or ELDR-C1del ELDR); (del ELDR: CRISPR/Cas9 with gRNAs specific to ELDR; ctrl: CRISPR/Cas9 with nontargeting gRNAs). Data are presented as mean + SD (panel O); ± SD (panels B,L). ∗P  < .05; ∗∗P  < .01; ∗∗∗P  < .001; ∗∗∗∗P < .0001. P values were calculated using Mann-Whitney U test (panels B-C); 1-way ANOVA with Holm-Šídák's for multiple comparisons test (panel E); log-rank Mantel-Cox test (panels F,I,M,Q); 1-way ANOVA with Dunnett's multiple comparisons test (panel H); “CGGC permutation test”30 number of permutations selected: 10 000 (panels L,O). s.c., subcutaneous; ns, not significant.

ELDR overexpression inhibits growth of AML in xenografts. (A) s.c. xenografts of ELDR-overexpressing THP-1 cell lines (ELDR-C1, ELDR-C3) and the EV control cell lines (EV1, EV2) in NSG mice. (B) Volume of tumors over time after the xenograft for ELDR-overexpressing line (ELDR-C1) and the EV1 control line measured by caliper. n = 6 mice in each group. (C) Weight of tumors at 4 weeks after the xenograft for ELDR-C1 and the EV1 control line. n = 6 mice in each group. (D) IV xenografts of ELDR-overexpressing THP-1 cell lines (ELDR-C1 and ELDR-C3) or EV1 control lines or NT THP-1 cells NT in NSG mice. (E) Percent of human CD45+ cells measured by FACS in organs of animals transplanted with the ELDR-C1 line or the EV1 control line 4 weeks after the IV xenograft. (F) Kaplan-Meier curve revealing disease-free survival after IV xenograft of the THP-1 ELDR-overexpressing cell lines ELDR-C1 and ELDR-C3 or the EV1 control line or NT cells as controls in NSG mice. n = 7 mice (ELDR-C1, ELDR-C3), n = 5 mice (EV1), n = 3 mice (NT); (statistical analysis: ELDR-C1 or ELDR-C3 vs EV1 or NT). (G) IV xenografts of the ELDR-overexpressing Mono-Mac-1 cell line (ELDR-C5, ELDR-C7) or the EV2 control line or NT Mono-Mac-1 cells (NT) in NSG mice. (H) Spleen weight of mice at 4 weeks after the xenograft that received ELDR-overexpressing Mono-Mac-1 cell lines ELDR-C5 and ELDR-C7 or the EV control cell line (EV2) or NT Mono-Mac-1 cells. n = 3 mice (EV2, ELDR-C5, ELDR-C7); n = 2 mice (NT). (I) Kaplan-Meier curve revealing disease-free survival of mice after an IV xenograft of the Mono-Mac-1 ELDR-overexpressing cell line ELDR-C5 or the EV2 and NT as controls in NSG mice. n = 6 mice (ELDR-C5), n = 3 mice (EV2), n = 3 mice (NT); (statistical analysis: ELDR-C5 vs EV2 or NT). (J) IV xenograft of ELDR-overexpressing cell line (ELDR-C1-Luc) or EV control line (EV-Luc) that also expresses a luciferase reporter gene into NSG mice. (K) Visualization of leukemic cells through monitoring of the luciferase signal. The figure illustrated is representative of the image captured on day 10 after IV injection and (L) quantification of radiance after the xenograft for the line ELDR-C1-Luc and the EV-Luc control line. n = 5 mice per group. (M) Kaplan-Meier curve revealing disease-free survival after IV xenograft of the THP-1 ELDR-overexpressing cell line ELDR-C1-Luc or the EV-Luc control line in NSG mice. n = 5 mice per group. (N) Visualization of leukemic cells (ELDR-C1-Luc) through monitoring of the luciferase signal after treatment of animals with LSD1i (GSK2879552)/ATRA or vehicle. The figure is representative of the image captured on day 18 of the treatment. (O) Quantification of radiance in mice after the xenograft of the line ELDR-C1-Luc and treatment of animals with LSD1i/ATRA or vehicle. n = 10 mice per group. (P) IV xenograft of ELDR-overexpressing THP-1 cell line (ELDR-C1ctrl) or the EV control cell line (EV1ctrl) vs ELDR-deleted cell line ELDR-C1del ELDR. (del ELDR: CRISPR/Cas9 with gRNAs specific to ELDR; ctrl: CRISPR/Cas9 with nontargeting gRNAs) into NSG mice. (Q) Kaplan-Meier curve for disease-free survival of mice after an IV xenograft of the ELDR-overexpressing cell line ELDR-C1ctrl vs the EV1ctrl and ELDR-C1delELDR as controls in NSG mice. n = 3 mice per group; (statistical analysis: ELDR-C1ctrl vs EV1ctrl or ELDR-C1del ELDR); (del ELDR: CRISPR/Cas9 with gRNAs specific to ELDR; ctrl: CRISPR/Cas9 with nontargeting gRNAs). Data are presented as mean + SD (panel O); ± SD (panels B,L). ∗P  < .05; ∗∗P  < .01; ∗∗∗P  < .001; ∗∗∗∗P < .0001. P values were calculated using Mann-Whitney U test (panels B-C); 1-way ANOVA with Holm-Šídák's for multiple comparisons test (panel E); log-rank Mantel-Cox test (panels F,I,M,Q); 1-way ANOVA with Dunnett's multiple comparisons test (panel H); “CGGC permutation test”30 number of permutations selected: 10 000 (panels L,O). s.c., subcutaneous; ns, not significant.

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