This prompted us to investigate the effect of PLK1 inhibition on primary tissues, where we observed that CB CD34+ cells are unaffected by volasertib ( Figure 3K). This effect was not unique to SEM cells because we observed similar results in RS4 11, an adult MLL-AF4+ ALL cell line that expressed similar levels of PLK1 ( Figures 3I and 3J). 48 h after treatment, half of the SEM cells were apoptotic, and at 72 h, very few viable cells remained ( Figure 3H). 24 h after treatment, there was an arrest in the G2/M phase of the cell cycle, resulting in decreased numbers of cells in the G0/1 and S phases ( Figures 3F and 3G). Although the two populations had a multitude of differences, we observed that none of the DE genes was reflective of a more proliferative nature of one population over the other, a key finding when considering consequences of each one of them being the cell of origin of the disease. A closer look at the genes more highly expressed in HSC/MPPs revealed stem cell signature genes such as MEIS1, HOXB2, and HMGA2 ( Figure S1I). As expected, LMPPs upregulated a number of genes required for lymphoid commitment, including AF4 ( AFF1), whereas HSC/MPPs had higher MLLT3 (AF9), another common MLL fusion partner ( Figure S1H). To further look into this question, we investigated the transcriptional differences between FL HSC/MPPs and LMPPs ( Table S1, tab 2). Showed that blasts from infant patients share a similar transcriptional profile with HSPCs (Lin−CD34+CD38−) which include HSC/MPPs and lymphoid-primed MPPs (LMPPs) however, they were unable to observe a closer transcriptional match between blasts and HSC/MPPs or LMPPs.
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