brd9 drug sensitivity  (MedChemExpress)

Journal: Leukemia

Article Title: The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia.

doi: 10.1038/s41375-024-02379-4

Figure Lengend Snippet: Fig. 2 Long-read RNA-sequencing validates the predicted alternative transcripts related to the ncBAF complex in SF3B1-mutated CLL. Sashimi plots illustrating the identified ASEs and alternative splicing patterns in four genes that encode ncBAF complex-related proteins in SF3B1WT versus SF3B1MUT CLL; ZEB1 and BRD9 exhibit the top two ASEs in the SE category, while DLST and SERBP1 showcase the top two ASEs in the A3SS category. Sashimi plots for other ncBAF complex-related genes, PLSCR1, TENT4B, CXXC1, DCAF16, and UBP1, are presented in Supplementary Fig. 3. For each gene, the top two sashimi plots within the gray box illustrate the predicted splice variants in SF3B1WT versus SF3B1MUT CLL. The colored arc highlights the primary ASE, while lighter arcs represent additional ASEs if present. The gene map indicates the relative location and order of the detected exons in relation to the sequencing results. For each corresponding gene, the lower two sashimi plots show the coverage and splice junction count data from the aligned long-read RNA-seq data from an SF3B1WT case (RS24) and an SF3B1MUT case (RS55), both belonging to subset #2 CLL. The direction of the genes is arranged from left to right. WT: wildtype; MUT: mutated; PSI: percent spliced in.

Article Snippet: Assessment of BRD9 drug sensitivity in CLL cell lines and primary CLL cells Cell lines and primary CLL cells were treated with BRD9 inhibitors/ degraders, I-BRD9 (SML1534; Sigma-Aldrich), PROTAC BRD9 Degrader-1 (HY-103632; MedChemExpress, New Jersey, NJ, USA), and dBRD9 Hydrochloride (SML2911; Sigma-Aldrich) [40, 41].

Techniques: RNA Sequencing, Alternative Splicing, Sequencing

Journal: Leukemia

Article Title: The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia.

doi: 10.1038/s41375-024-02379-4

Figure Lengend Snippet: Fig. 7 BRD9 inhibition induces potent pro-apoptotic effects in primary CLL cells. A Dose-response analysis of I-BRD9 treatment in 3 SF3B1WT (SKL48, SKL152, SKL53) and 3 SF3B1MUT (SKL147, SKL47, SKL157) primary CLL cell samples. The cell lines were treated with drug concentrations ranging from 0.001 to 50 µM for 2 days, and cell viability was determined by CellTiter-Glo 2.0. Dose-response curves are shown with 95% confidence intervals, while individual dots display the mean values of triplicates, with error bars representing the standard deviation. B Stacked density plots showing apoptosis assessment in the same primary CLL cell samples as in (A). Treatment with 5 µM Camptothecin and vehicle (DMSO) were used as the positive and negative controls, respectively. Apoptosis was evaluated by Annexin V/PI staining and subsequent flow cytometry analysis. The lower left (Annexin V-/PI- cells), upper left (Annexin V+/PI- cells), and upper right (Annexin V+/PI+ cells) quadrants in the density plots represent the percentages of viable, early apoptotic, and late apoptotic cells, respectively. C Stacked bar plot displaying differences in the percentages of viable, early apoptotic, and late apoptotic cells compared to negative controls with corresponding P values (Student’s t-test). The bar plot displays the mean values, with error bars representing the standard deviation. WT: wildtype; MUT: mutated; IC50: half-maximal inhibitory concentration; RLU: relative luminescence unit.

Article Snippet: Assessment of BRD9 drug sensitivity in CLL cell lines and primary CLL cells Cell lines and primary CLL cells were treated with BRD9 inhibitors/ degraders, I-BRD9 (SML1534; Sigma-Aldrich), PROTAC BRD9 Degrader-1 (HY-103632; MedChemExpress, New Jersey, NJ, USA), and dBRD9 Hydrochloride (SML2911; Sigma-Aldrich) [40, 41].

Techniques: Inhibition, Standard Deviation, Staining, Cytometry, Concentration Assay