Modeling of myeloid leukemia using CRISPR/Cas9 and sgRNA targeting Tet2 and/or Tet3. (A) Schematic diagram of in vivo transformation of primary HSPCs. (B) Kaplan-Meier survival curve of mice that received transplantation with HSPCs infected with empty control, Tet2 sgRNA only, Tet3 sgRNA only, and Tet2/Tet3 sgRNAs. n = 7 per group; ∗∗∗P < .0001. (C) Characterization of myeloid leukemia in various hematopoietic organs. Representative fluorescence-activated cell sorting (FACS) plot of various hematopoietic organs, picture showing splenomegaly and enlarged lymph node, histology section of the bone marrow, and cytospin of leukemic cells. (D) Allelic examples of dominating leukemia clones with Tet2 and Tet3 loss-of-function in different biological replicates. Indels, insertion/deletions.