Journal: Blood Advances

Article Title: Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia

doi: 10.1182/bloodadvances.2019030916

Figure Lengend Snippet: Pharmacodynamic response of MIC-1 and p53 target gene expression during treatment with AMG 232. Mean (±standard error) ratio of posttreatment vs pretreatment serum MIC-1 in arm 1 (A) and arm 2 (B). (C) Fold change from baseline in expression of BAX, PUMA, P21, MDM2, and TP53 genes in bone marrow. EOT, end of treatment.

Article Snippet: For p53 target gene assessment, bone marrow aspirates collected in PAXgene Bone Marrow RNA tubes (PreAnalytiX GmbH) were stored at −20°C.

Techniques: Targeted Gene Expression, Expressing

Journal: Blood Advances

Article Title: Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia

doi: 10.1182/bloodadvances.2019030916

Figure Lengend Snippet: Activity of AMG 232 with or without trametinib. (A) Maximum change from baseline in bone marrow blast percentage and best overall response in 24 evaluable patients in arm 1 (AMG 232 monotherapy) and arm 2 (AMG 232 + trametinib). Unevaluable patients either had no baseline measurement for bone marrow blast count or only 1 measurement in total. (B) Median treatment duration of responders (blue bars; n = 6) and nonresponders (red bars; n = 24). In both panels, dose cohorts are shown next to each bar, and TP53 mutation status, when evaluated in patients with unknown status at screening, is shown as positive (+) or negative (−). PD, progressive disease; TF, treatment failure.

Article Snippet: For p53 target gene assessment, bone marrow aspirates collected in PAXgene Bone Marrow RNA tubes (PreAnalytiX GmbH) were stored at −20°C.

Techniques: Activity Assay, Mutagenesis

Journal: Nature Communications

Article Title: Dasatinib overcomes glucocorticoid resistance in B-cell acute lymphoblastic leukemia

doi: 10.1038/s41467-023-38456-y

Figure Lengend Snippet: A Flow cytometry gating strategy used to sort B-cell developmental populations (pre-pro-B: CD34 + /CD38 + /TdT + /CD24 - ; pro-B: CD34 low /CD38 + /TdT - /CD24 + ; pre-B: CD34 - /CD38 + /TdT - /CD24 + ) in three healthy bone marrow donors for RNA-Seq analysis. B Canonical pathways are significantly enriched during development. Pathways highly correlated with BCR signaling were plotted; bold indicates BCR and glucocorticoid-related pathways. Heatmap is colored based on the z -score of IPA results. C Upstream regulators across development correlated with BCR complex; bold indicates BCR and glucocorticoid-related pathways. Heatmap is colored based on the z -score of IPA results. D Experimental workflow of healthy bone marrow donors analyzed by CyTOF. E Scaled median expression of B-cell related proteins and glucocorticoid receptor (GCR) in healthy pre-pro-B, pro-B, and pre-B cells. F GCR expression (Mean ± SEM) across cell cycle states ( n = 3 healthy donors). Kruskal–Wallis nonparametric test is used to test significance (α = 0.05); G0 vs S p = 0.0285; G0 vs G2 p = 0.0358; S vs M p = 0.0225; G2 vs M p = 0.0255. G Mean percentage of each cell cycle phase in vehicle (ethanol) and dexamethasone (dex, 1 µM) treated cells. Paired t -test dexamethasone vs vehicle: G0: p = 0.0005, G1: p = 0.0021; S: p = 0.0789. H Percentage of live cells (cCASP3 - /cPARP - ) in vehicle (ethanol) and dexamethasone (1 μM) treated healthy cells ( n = 3 healthy donors). Two-tailed paired t -test was used to test significance, p = 0.0742, not significant. Asterisks indicate p values as calculated by a two-tailed t -test (* p ≤ 0.5; ** p ≤ 0.01; *** p ≤ 0.001; n.s. not significant). Source data are provided as a Source Data file. The experimental workflow was created with Biorender.com.

Article Snippet: Healthy human bone marrow samples ( n = 3 for RNA-Seq, n = 4 for CyTOF) were purchased through AllCells.

Techniques: Flow Cytometry, RNA Sequencing, Expressing, Two Tailed Test