Xenograft Model of Leukemia

All animal experiments were performed with the approval of Dana-Farber Cancer Institute's Institutional Animal Care and Use Committee. NOD.Cg-Prkdc^scid Il2rg^tm1Sug/JicTac (NOG) mice were obtained from Taconic Biosciences. Nonirradiated 8- to 12-week-old adult mice were transplanted with previously established PDXs (25 (link)) via tail-vein injection (250,000 cells/mouse). Engraftment of human cells (hCD45⁺) was analyzed and monitored longitudinally by weekly bleeding to quantify hCD45⁺ cells in the peripheral blood by flow cytometry with human CD45-PE and anti-mouse CD45-APC-Cy7 antibodies (BioLegend). Mice were monitored closely to detect disease onset, and treatment started when hCD45⁺ cells were detectable in the peripheral blood. Mice were randomly assigned to either normal or 0.1% VTP-50469 rodent special diet (25 (link)). Mice were bled weekly to monitor leukemia burden as described above and euthanized when showing clinical signs of disease (experimental endpoint). Leukemia cells from a subset of these animals were harvested after 7 days of treatment to perform RNA-seq.