Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy - Nature Medicine

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Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy - Nature Medicine
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To raise awareness of StemCellAwarenessDay, here is a study investigating the role of stemcell architecture in driving myelodysplastic syndrome progression and predicts response to venetoclax based therapy

competitor BM cells. Donor-derived PB reconstitution was assessed 6 weeks after transplantation, and mice with similar mean chimerism were randomized to treatment groups.

At the end of treatment, the mice were killed and autopsied, and their rear legs and, occasionally, spleens were resected for analysis. For BM biopsies, tibias and spleens were fixed in 10% neutral-buffered formalin overnight, decalcified in Cal-Ex for 24 h, and then transferred into 70% ethanol and stored at room temperature for a minimum of 24 h for dehydration. Fixed tissues were embedded in paraffin according to standard protocols.

BMS-345541 was purchased from Selleck Chemicals. For in vitro experiments, BMS-345541 was reconstituted in DMSO and diluted in sterile PBS. Cells were treated with 5 μM BMS-345541. For in vivo experiments, suspensions of BMS-345541 in a mix of DMSO, PEG 300, Tween 80 and water were freshly prepared and stored at RT. BMS-345541 was administered every other day by gavage at 75 mg per kilogram body weight per day for 3 weeks .

At Washington University in St. Louis, data were imported and aligned to the human reference using the Burrows–Wheeler Aligner -MEM alignment algorithm . Duplicate reads were tagged using Picard MarkDuplicates . Somatic mutations were called using the genome/analysis-workflow somatic exome processing pipeline . Somatic variants were annotated using the Ensembl Variant Effect Predictor . The entire pipeline is available on GitHub . Only high-confidence variants were considered.

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