Immune profiling in mice treated with BCL2 or JAK1/2 inhibitors

This study examined the impact of venetoclax or ruxolitinib on the immune profile of the bone marrow in treated mice showing venetoclax reduced expression of MHC-II and IFNg associated genes while ruxolitinib upregulated MHC-II and downregulated IFNg associated genes. The BCL2 inhibitor venetoclax and JAK1/2 inhibitor ruxolitinib (SelleckChem, Houston, TX) were used to treat C57BL/6 WT mice for two days. Venetoclax (100 mg/ml) and its vehicle (60% phosal R 50 PG (Merck, Germany), 30% polyethylene glycol (PEG) 400 (Merck, Germany), 10% ethanol) were administered by oral gavage once daily for two days. Ruxolitinib (180 mg/ml) and its vehicle (2% DMSO, 30% PEG 300 (Merck, Germany), ddH2O) were administered twice a day by oral gavage for two days. Total BM RNA was extracted from cohorts of mice (n=3-4) days 1, 3 and 7 post-drug treatment or from untreated controls using the Qiagen RNeasy Kit (Qiagen, Venlo, The Netherlands). Gene expression was determined using the NanoString Mouse Immunology Panel (NanoString Technologies, Seattle, WA) as per manufacturer’s instructions. All raw data was reviewed, and all samples in downstream analysis had no quality control flags and detection of at least 20% of probes. All experiments were normalised and analysed using nCounter Advanced Analysis (version 2.0.115; NanoString Technologies).