Animal models

Female FVB/N and C57Bl/6Nj mice (6 weeks old) were purchased from Janvier Labs. Bone marrows from MRP8-PML/RARA transgenics⁷⁰ (P/R) crossed with FTL3ki⁶⁶ (P/R-FLT3ki) were injected in CD45.2 congenic FVB/N-strain syngenic mice. PML/RARAC212S immortalization of primary hematopoietic progenitors was performed as previously.⁷¹ Briefly, lineage-depleted (Lin⁻) mouse bone marrow hematopoietic cells collected from 5-fluorouracil-treated C57Bl/6Nj Pml^+/+ or Pml^−/− mice were infected with retroviruses obtained by transient transfection of Plat-E cells with pMSCV-PML/RARAC212S and pMIE-FLT3-ITD. After spinoculation, transduced cells were injected in C57Bl/6Nj syngenic mice. For experiments, 1 × 10⁶ leukemic bone marrow cells were intravenously injected into recipient mice. Retinoic acid (ATRA) was administered by subcutaneous implantation of 21-day-release 10-mg pellets (Innovative Research of America). Arsenic (concentration 1 mg/mL, injected dose 5 µg/g body weight; ACROS Organics) was administered by daily intraperitoneal injection.