Page 297 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
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Figure 2. Genetic and pharmacological inhibition of DYRK1A decreases growth of Down syndrome acute lymphoblastic leukemia cells. (A) Ratio of wild-type (WT)-KRASG12D and Tc1-KRASG12D transduced with GFP-expressing Banshee vectors encoding two shDyrk1a compared to empty Banshee-U6 counterparts over 9 days (N=4 replicates); ***P<0.001. (B) Validation of Dyrk1a knock- down at the protein level 48 hours after transduction (GFP-sorted). Dyrk1a band intensities were quantified and normalized as a ratio of shDyrk1a-transduced to control U6-transduced WT-KRASG12D cells. (C) Cytotoxic effect of increasing doses (in μM) of the DYRK1A inhibitors EHT1610, AM30, Leucettinib-21 (LCTB-21) and its inactive isomer iso-Leucettinib-21 (Iso LCTB-21) at 48 hours in murine WT-KRASG12D and Tc1-KRASG12D cells assessed by flow cytometry (Annexin V staining). (D) Dose-response curves assessing efficacy of EHT1610, LCTB-21 and Iso LCTB-21 at 72 hours by alamarBlue cell viability assay in murine WT-KRASG12D and Tc1-KRASG12D cells. (E) Heatmap integrating relative half-maximal inhibitory concentration (IC50) values obtained for the DYRK1A inhibitors tested in our murine cell lines.
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