Page 305 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
Haematologica | 109 July 2024
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ABCD
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Figure 2. Dormant minimal residual disease cells arise from subpopulations present at diagnosis and the CREB inhibitor 666-15 is cytotoxic in T-cell acute lym- phoblastic leukemia cells. Uniform manifold approximation and projection (UMAP) of acute lymphoblastic leukemia (ALL) cells generated using intracellular anti- body signals showing cluster segregation in presentation (red) and minimal residual disease (MRD) (blue) samples (A). UMAP of ALL cells showing scaled expression of pCREB (B) and Ki67 (C). UMAP of ALL cells in individual patients showing Ki67 levels in paired presentation and MRD time points (D). UMAP of ALL cells showing cluster distribution in presentation (E) and MRD samples (F). Histogram of 666-15 half maximal inhibitory concentration (IC50) in patient-derived xenografts (PDX) on MSC and MSCs alone (mean ± standard deviation [SD] are shown (G). Histogram of percentage of apoptotic cells as measured by annexin V binding in cells dosed for 48 hours with control vehicle (CV) or 2 different doses of 666-15 in triplicate PDX (H). Histogram showing the normalized frequency of cells in various stages of the cell cycle in cells dosed for 48 hours with CV or 2 different doses of 666-15 in triplicate PDX. Mean ± SD are shown. **Denotes statistical significance where P<0.01.