Figure 5.

Cell cycle arrest and cell death in MLL-AF9-expressing cells. Propidium iodide cell cycle analysis was performed on cells cultured at the same initial density (3 × 10⁵ cells per ml) for 72 hr in the presence (Left) or absence (Right) of tetracycline. Cell cycle progression was unaffected by tetracycline withdrawal in parental U937T cells. Expression of MLL-AF9 was associated with marked cell death as evidenced by the large sub-2N population. The vast majority of cells in these cultures were morphologically degenerated and not viable as assessed by trypan blue exclusion. The viable population in these cultures was composed of small numbers of macrophages (see Fig. 6). Expression of the amino-terminal portion of MLL containing either 3 or 2 AT hook motifs (MLL3AT or MLL2AT, respectively) results in cell cycle arrest in G₀/G₁ without appreciable cell death. Morphologically and immunophenotypically these cells showed evidence of partial differentiation toward macrophages (Figs. 6 and 7).