Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia (original) (raw)
Figure 8
Sensitivity of MLL cells to CDK inhibition.
(A) Effect of flavopiridol. Top panel: seven MLL cell lines (red lines) and four control leukemia lines of different etiology (black lines) were treated with increasing concentrations of flavopiridol as indicated. Proliferation was photometrically assessed in triplicate samples by MTT reduction. For better comparison, all optical density at 550 nm (OD550) readings were normalized to yield one unit in the absence of inhibitor. Mean values are plotted semilogarithmically against flavopiridol concentrations. To avoid clutter, standard deviations are indicated only for drug concentrations where MLL and control cell lines diverge in response to treatment. (B). Effect of alsterpaullone. Alsterpaullone was tested like described for (A). (C) Effect of flavopiridol and alsterpaullone on primary hematopoietic cells. Triplicate samples of mouse bone marrow cells enriched in early precursors by 5-fluorouracil treatment of the donors were cultured in liquid medium supplemented with IL-3, GM-CSF, IL-6, SCF, and the indicated amount of flavopiridol or alsterpaullone (black line). Proliferation was measured by MTT reduction. For comparison, precursor cells were retrovirally transduced with MLL-ENL, and the resulting lines were tested again for drug sensitivity under identical culture conditions (red line). Given are mean values and standard deviations of triplicates.