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. 2019 Nov 26;34(5):1241–1252. doi: 10.1038/s41375-019-0653-z

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© The Author(s) 2019

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Loss of SKP2 attenuates Notch-induced leukemia. Lin⁻ cells from Skp2^+/+, Skp2^+/−, or Skp2^−/− (CD45.2) mice were transduced with MSCV-GFP (Vector), MSCV-ICN1-GFP (ICN), or MSCV-N1ΔEGFΔLNRΔP-GFP (N1ΔEGF) constructs. 2.5 × 10⁴ GFP⁺ cells were transplanted into lethally irradiated BoyJ (CD45.1) recipients (three independent experiments) and were analyzed for: a Percentage of DP T-cells in in gated CD45.2⁺ donor cells in PB. Skp2^+/+ Vector (n = 6), Skp2^+/+ ICN (n = 10), Skp2^+/− ICN (n = 10) and Skp2^−/− ICN (n = 6); (average ± SE). b Bar graph show BrdU incorporation in GFP⁺ cells from Skp2^+/+ ICN (n = 5) and Skp2^−/− ICN (n = 3) in BM and spleen populations analyzed in recipients at week 8 from transplant. c Kaplan–Meier survival curve. Control cohorts include: Skp2^+/+ Vector group (n = 10; green solid line) and Skp2^−/− nontransduced and Skp2^−/− Vector group (n = 8; dark green dashed line); all these groups behaved identically. Experimental cohorts: in left panel include Skp2^+/+ ICN (n = 19; blue line), Skp2^−/+ ICN (n = 14; purple line) and Skp2^−/− ICN (n = 14; red line); in right panel includes Skp2^+/+ N1ΔEGF (n = 6; blue line) and for Skp2^−/− N1ΔEGF (n = 6; red line). d Scheme representing the survival percentages of Skp2^−/− ICN^ns (solid red) and Skp2^−/− ICN^s (dashed red). Mice within Skp2^−/− ICN genotype were distributed in two groups based on their survival, here called Skp2^−/− ICN^ns (no survivors; 71%) and Skp2^−/− ICN^s (survivors; 29%). Recipients of all genotypes (in three independent experiments), were analyzed at full-blown disease or at 1 year from transplant. e Line graph in left panel represents counts of WBC in the PB of recipient mice at the time points indicated. Line graph in right panel represents percentage of GFP⁺ cells gated on CD45.2⁺ cells in the PB of recipient mice at the time points indicated (average ± SE). Skp2^+/+ Vector (n = 6), Skp2^+/+ ICN (n = 10), Skp2^−/− ICN^ns (n = 6), and Skp2^−/− ICN^s (n = 3). Arrows indicates point of divergence between Skp2^−/− ICN^s and Skp2^−/− ICN^ns. All results are expressed as average ± SD unless otherwise indicated. *p < 0.05, **p < 0.01, ***p < 0.005 by two-sample t-test, t-test or log-rank test