Fig. 1: HSF1 is required for the initiation and maintenance of MLL-AF9–induced AML.
From: HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia
a Survival curve of mice receiving MLL-AF9 transduced LSK (Lin–cKit+Sca1+) cells from Hsf1fl/fl (Con) or Hsf1fl/flVav-Cre + (Hsf1KO) mice (n = 5 mice/group). Log-rank test, *p = 0.0021. b Scheme of serial plating for establishing immortalized leukemia cells. c MLL-AF9 Hsf1fl/flcreER leukemia cell numbers in the presence or absence (vehicle, Con) of 4-hydroxytamoxifen (the active metabolite of tamoxifen, 4-OHT, 200 nM). 1 × 103 leukemia cells were plated and counted 3–4 days later (n = 6 independent replicates). *p = 2.5 × 10−5. d Colony numbers formed in the presence or absence of 4-OHT (n = 8 independent replicates). *p = 7.3 × 10−6. e 500 cells from vehicle (Con) or 4-OHT treated colony assay (d) were replated without further 4-OHT treatment (n = 6 independent replicates). *p = 4.24 × 10−7. f Scheme of establishment of MLL-AF9–induced AML and delivery of tamoxifen to induce Hsf1 deletion. g Survival curve of mice receiving MLL-AF9–transduced LSK cells from Hsf1+/+creER or Hsf1fl/flcreER mice with or without Tam treatment (n = 8 mice/group). Log-rank test, *p = 0.0002. h Frequencies of LSCs in MLL-AF9 Hsf1fl/flcreER leukemic mice with or without Tam treatment (n = 4 independent replicates). *p = 2.2 × 10−5, **p = 0.017. i Frequencies of CD11b+ leukemia cells in MLL-AF9 Hsf1fl/flcreER leukemic mice with or without Tam treatment (n = 3 independent replicates). *p = 2.79 × 10−5. In (c–e, h, i), two-tailed t test was used, data are presented as mean values ± SEM. j Wright-Giemsa staining of LSC-derived colony forming cells with or without 4-OHT treatment (n = 3 independent replicates). Note that Tam treatment induced LSC differentiation with reduced nuclear to cytoplasmic ratio. Scale bar, 5 μM. k Survival curve of mice receiving LSCs from full-blown MLL-AF9 Hsf1fl/flcreER leukemic mice treated with or without Tam (n = 5 mice/group). Log-rank test, *p = 0.0019. l Survival curve of mice receiving LSCs from full-blown MLL-AF9 Hsf1fl/flcreER leukemic mice treated with two cycles of Tam (n = 5 mice/group). Log-rank test, *p = 0.0031. Source data are provided as a Source Data file.
