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. 2024 Jan 27;15:828. doi: 10.1038/s41467-023-44348-y

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a LSD1 expression in CR and SD in the BM analyzed by WB using specific anti-LSD1 antibody (representative of 3 independent experiments). b Effect of LSD1i on survival of APL-bearing mice. Schematic representation (upper panel) and Kaplan–Meier survival curve (lower panel) after LSD1 inhibition under SD and CR diet. Median survival in days and p values, with SD as a common control (log-rank test, Bonferroni-adjusted) are indicated. SD+LSD1i (n = 5), CR (n = 8; vehicle), CR+LSD1i (n = 9), SD (n = 6; vehicle). Quantification of total numbers of APL-blast (in c by FACS; SD, n = 3; CR, n = 6; SD+LSD1i, n = 2; CR+LSD1i, n = 6) and frequency of apoptotic cells (in d; SD, n = 3; CR, n = 3; SD+LSD1i, n = 4; CR+LSD1i, n = 4; the SD and CR group is same in Supplementary Fig 1l. e Impact of CR on growth of NB4 cells. Upper panel: experimental scheme. NSG mice injected subcutaneously with 10⁶ WT (wild-type) (left flank) or LSD1 KO (knockout) (right flank) NB4 cells, fed SD (n = 6) or CR (n = 5), sacrificed after 20 days to measure tumor volume (lower left panel) and mass (lower right panel). f Kaplan–Meier survival curves of APL recipient mice subjected to vehicle (40% PEG), rapamycin (RAPA) (4 mg/kg) or OSI-906 (20 mg/kg), alone or in combination with LSD1i (DDP37368) (45 mg/kg). The median survival in days and P values, with SD as a common control (log-rank test, Bonferroni-adjusted) are indicated. RAPA (n = 4), OSI-906 (n = 4), SD+LSD1i (n = 4), RAPA+ LSD1i (n = 3), OSI-906 + LSD1i (n = 4) with SD (n = 7; vehicle). g Effect of OSI-906 treatment on NB4-cell growth in vitro (n = 3 biological replicates). Data are expressed as mean ± SD, one way (for c–e, h) and two-way (g) ANOVA with post-hoc Tukey’s multiple comparison. ‘n’ represents number of mice/groups for b–f, adjusted p values indicated. h Effect of OSI-906 treatment and LSD1 ablation on NB4 colony formation (two separate sets of experiments, n = 4 biological replicates for WT NB4, left panel, n = 3 biological replicates for LSD1 KO cells, right panel). For h, data are normalized on the average of the relative untreated control and expressed as mean ± SD. Source data are provided as a Source Data file.