Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations
J. Clin. Invest. Adrienne M. Dorrance, et al. 116:2707 doi:10.1172/JCI25546 [Go to this article.]

Figure 6
Evaluation of progenitor populations in Mll^PTD/WT splenocytes compared with Mll^WT/WT sex-matched littermate controls. (A) Results from CFU assays to assess progenitors of erythroid (BFU-E), granulocytic, erythroid, monocytic, megakaryocytic (GEMM-CFU), and granulocyte, macrophage (GM-CFU) lineages show significantly increased CFUs derived from Mll^PTD/WT versus Mll^WT/WT splenocytes. *P = 0.03; **P = 0.0025. Error bars indicate SD. Splenocytes from (B) Mll^WT/WT and (C) Mll^PTD/WT mice (n = 8 mice per genotype) show increased surface density expression of the erythroid marker Ter119 in Mll^PTD/WT mice. Ter PE, PE fluorochrome–conjugated Ter119. Secondary splenic colonies from (D) Mll^WT/WT, (E) Mll^Af9/WT, and (F) Mll^PTD/WT mice (n = 6 mice per genotype, plated in duplicate). The numbers of secondary colonies per plate (~230) were similar between genotypes. The number of cells per colony was dramatically increased in Mll^PTD/WT mice compared with Mll^WT/WT or Mll^Af9/WT mice. (G–I) Primary CFU progenitor cells harvested after 14 days and maintained in liquid cultures for 18 days, supplemented with SCF, IL-3, and IL-6, and in the presence of BrdU for the last 4 days. An anti-BrdU antibody gated on viable cells demonstrates a smaller fraction of Mll^WT/WT cells proliferating (G) compared with Mll^PTD/WT cells (H). Assessment of programmed cell death (I, upper right and lower right quadrants) revealed a sizeable fraction (~50%) of Mll^PTD/WT progenitors undergoing apoptosis during expansion. While a significant fraction of Mll^PTD/WT cells were proliferating, approximately 50% were undergoing apoptosis. In 2 additional experiments, the Mll^WT/WT cells had already died by this time point in culture (see Table 3), precluding a statistical comparison of these results in G–I.