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. Author manuscript; available in PMC: 2017 Jul 11.
Published in final edited form as: Cancer Cell. 2016 Jun 23;30(1):92–107. doi: 10.1016/j.ccell.2016.05.008

Figure 2. R882-mutated DNMT3A establishes leukemia-initiating stem cells (LSCs) ex vivo in the presence of activated RAS.

Figure 2

(A) FACS analysis of in vitro immortalized progenitors by RH-RAS using a liquid culture system.

(B) Wright–Giemsa staining (upper) and FACS analysis of RH-RAS-immortalized progenitors 14 days post-cultivation with indicated cytokines. FACS control, non-specific IgG (grey, open); Scale bar, 10 μm.

(C) Kaplan-Meier curve of mice receiving primary or secondary BMT with RH-RAS induced leukemia.

(D) Kaplan-Meier curve of mice (n = 5–6) receiving BMT of the indicated numbers of RH-RAS immortalized cells.

(E) Hierarchical clustering of genome-wide H3K4me1 profiles of LSCsRH-RAS, AML-causing LSC lines produced by overexpressed HOXA9 plus MEIS1 (HOXA9-MEIS1), and various normal blood cell types. LT-HSC, long-term HSC; ST-HSC, short-term HSC; MPP, multipotent progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; GMP, granulocyte-monocyte progenitor; MEP, megakaryocyte-erythroid progenitor; Mac, macrophage; Mono, monocyte; GN, granulocyte; B, B220+/CD19+ B-cell; CD4/8, CD4/8+ T-cell; NK, natural killer cell; EryA and EryB, Ter119+/CD71+ erythroid cell with high and low forward scatter, respectively.

(F) Principal component (PC) analysis of transcriptome profiles of LSCsRH-RAS and various normal blood cell types. Besides what is described in panel E, CD34−KLS, Cd34−/c-Kit+/Lin−/ScaI+ HSC; MPP1, Flk2− multipotent progenitor; MPP2, Flk2+ multipotent progenitor; NKT, natural killer T-cell; Ery, erythroid cell.

See also Figure S2.