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. Author manuscript; available in PMC: 2010 Oct 7.
Published in final edited form as: Nature. 2009 Nov 12;462(7270):182–188. doi: 10.1038/nature08543

Figure 4. SAHM1 reduces T-ALL proliferation and leukaemic initiation potential.

Figure 4

a, Growth effects of SAHMs on a panel of human T-ALL cell lines of known mutational status. Cells were incubated with 15 µM DAPT (blue triangles), SAHM1 (red squares), SAHM1-D1 (green diamonds) or DMSO (black circles) and monitored for proliferation after 3 and 6 days of culture. Data points are mean ± s.d. (n = 3). b, Effects of SAHMs on apoptosis of T-ALL cells monitored using Capase-glo 3/7 (Promega) in cultures carried out as in a. Error bars, s.d. c, d, Ex-vivo treatment of L1601PΔP cells with SAHM1 (5 µM, 12 h) limits leukaemia initiation in secondary murine recipients. Reduction of spleen weight in the SAHM1 cohort (n = 6) compared to vehicle (n = 6) at the first sign of disease toxicity (23 days) (P = 0.001) (c). Circulating GFP-positive cell count in the blood is reduced by ~100-fold in the SAHM1 cohort (n = 6) relative to vehicle (n = 6) (P = 0.0026) (d). Error bars, s.d. Statistical analyses performed with a two-tailed t-test. *P < 0.01, **P < 0.005. e, An immunohistochemical stain for GFP that imparts a brown colour shows extensive leukaemic infiltration of bone marrow (BM) and spleen (SPL) in representative mice receiving vehicle-treated transplants relative to SAHM1. SPL, spleen. Scale bars,