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. Author manuscript; available in PMC: 2015 Apr 23.
Published in final edited form as: Nature. 2014 Aug 17;514(7523):513–517. doi: 10.1038/nature13605

Extended Data Figure 5. Utx is a tumor suppressor and genetically inactivated in T-ALL Utx whereas is dispensable for physiological T cell development.

Extended Data Figure 5

a, b, Study of lymphoid development on Utx−/Y compared to Utx+/+ (or UTX+/Y, not shown) background. FACS analyses for CD4+ and CD8+ expression (a) and the relative proportions of CD4+, CD8+ double positive thymocytes across different genotypes (b) are shown. A representative example of three independent samples (biological replicates) is shown. c, Illustration of the transplantations scheme for the in vivo leukemia studies. d, e, T-ALL progresses faster in the male knockout background for Utx (Utx−/y) compared to female wildtype background (Utx+/+), in Notch1-IC/GFP, as it is demonstrated by white blood counts (d) in the peripheral blood as well as GFP+ cells representation upon transplantation of wild type progenitors (e) from female mice (Utx+/+) compared to the corresponding knock-out cells (Utx−/y). f, Survival study of the recipients for male wild-type (Utx+/Y, n=7) and knock-out (Utx−/Y, n=5) mice expressing Notch1-deltaE(ΔE)/GFP (the allele with the weaker oncogenic action compared to Notch1-IC). g, h, Survival analysis of recipients upon transplantation of wild type progenitors from female mice (Utx+/+) compared to the corresponding knock-out cells (Utx−/y) infected with N1-IC (g) or N1-ΔE (h). i, qPCR validation of expression levels of one down-regulated (Suz12) and one up-regulated (Il7ra) gene in Utx−/Y (compared to UTX+/Y). The average of three independent samples/studies is presented. j, Targeted Sanger sequencing in pediatric led to identification of three cases with frameshift mutations. The positions of mutations are indicated by dashed lines in the electropherograms. k, Identification of one in-frame deletion (p.A14_A17del, #1, top panel), one splice acceptor site (#2, second panel) and one missense mutation (#3, third panel) in adult T-ALL. #4 is an adult T-ALL case with wild-type UTX (control, bottom panel). Mutations are indicated by red-colored characters. l, Levels of UTX in CUTLL1 T-ALL cells in the absence (−dox) or presence (+dox) of doxycycline. m, n, Apoptosis analysis through measuring annexin-V staining using control LacZ-expressing and UTX-expressing CUTLL1 in the absence (−dox) or presence (+dox) of doxycycline. Representative plots (l, n) as well as average representation (l, m) of three independent experiments are shown.