Fig. 1. B Cell Differentiation and Response to BH3 Mimetics and PIM Kinase Inhibition.

a mRNA and protein levels during B cell differentiation across subsets and time points. Data are shown as floating bars (min to max, mean as line) for NBC (n = 3) and as box plots (median ± IQR, whiskers min to max) for d4 aBC (n = 4), CD23+ aBC (n = 5), PB (n = 5), and ePC (n = 5). b Protein levels across B cell and PC subsets. Samples derived from the same experiment with two different processed gels, including one for pBAD, BAD, and BIM (same gel of Fig. 1a), and another for NOXA. The blot is representative of 2 independent experiments. c Schematic of the assay design during B cell differentiation: cells were treated at specified time points with BH3-mimetic molecules and AZD1208. Data are representative of one experiment. Cell viability was assessed by flow cytometry. Percentage of cell viability were normalized to control condition and IC₅₀ were calculated. d RNAseq expression of anti-apoptotic factors and PIM kinases in 33 MMCLs. Data are shown as mean (n = 33, ‘n’ denotes the number of distinct MMLs). e CRISPR screening data from DepMap in 17 MMCLs: dependency scores showing stronger dependency on PIM2 and MCL1 than on BCL-XL and BCL2. No dependency was observed for PIM1 or PIM3. Data are shown as mean (n = 17, ‘n’ denotes the number of distinct MMLs). f Protein levels of antiapoptotic and proapoptotic factors in MMCLs. Samples derived from the same experiment with different processed gels, including one for PIM2, MCL1, BCLXL, BCL2, p-BAD, BAD, BIM, NOXA and another for BAK, BAX. The blot is representative of 2 independent experiments. g Cell viability in MMCLs after treatment with BH3-mimetics and AZD1208, with calculated IC₅₀ values. Data are shown as mean +/− SEM (Venetoclax, n = 3; AZD5991 and  AZD1208, n = 4; A1155463, n = 2). NBC, naïve B cell; d4 aBC, day-4 activated B cell; CD23+ aBC, CD23-positive activated B cell; PB, plasmablast; ePC, early plasma cell; MMCLs, multiple myeloma cell lines; PIMi, pan-PIM inhibitor AZD1208. “n”, denotes the number of biological replicates except for Fig. 1d and Fig. 1e as indicated. Source data are provided as a Source Data file.