Fig. 1.

MYC activation is associated with low BCL2 expression. a MYC paralog expression (TPM) and copy number variation (CNV) in human small cell lung cancer (SCLC) cell lines (n = 42). b MYC paralog expression in SCLC patients. Center line (median), lower/upper box hinges (25th/75th percentile), whiskers extend to the most extreme value within 1.5× interquartile range (IQR) of the hinges. c CRISPRa system for transcriptional upregulation of Myc paralogs (top). Expression (z-scores) of Myc paralogs and Myc target genes in CRISPRa cells (bottom). d Western blot showing MYC and MYCN in Myc- and Mycn-activated CRISPRa cells compared to mock control. HSP90 was used as a loading control. e Viability screening of Myc-activated CRISPRa cells treated with alisertib for 96 h (n = 3). f Differentially upregulated and downregulated genes (sorted by log₂ fold-change) in human SCLC cell lines (n = 42) with high MYC (n = 22) vs. low MYC (n = 20) expression. g Western blot of ASCL1 and BCL2 in MYC paralog-amplified human SCLC cell lines (n = 9). HSP90 was used as a loading control. h Immunohistochemical staining of MYC and BCL2 in tumors of SCLC patients with high MYC (left) or high BCL2 (right) expression (percentage of patients in the cohort (n = 49) with high BCL2 or MYC levels is indicated. Scale bar = 100 µm). i Bcl2 expression (counts normalized to library size) in Myc paralog-activated CRISPRa cells. Benjamini–Hochberg-adjusted p values for Myc paralogs were obtained as contrasts of a global differential expression test. j Western blot showing BCL2 levels in MYC-amplified H82 and H524 cells ± BCL2 overexpression. HSP90 was used as a loading control. k GI₅₀ values of MYC-amplified H82 and H524 cells ± BCL2 overexpression treated with alisertib for 72 h (n = 3). l Western blot of BCL2 in Myc-activated CRISPRa cells ± BCL2 overexpression. HSP90 was used as a loading control. m GI₅₀ values of Myc-activated CRISPRa cells ± BCL2 overexpression treated with alisertib alone or in combination with 500 nM venetoclax (BCL2i; n = 3). Error bars indicate mean ± SEM. Two-tailed unpaired t tests, ****p < 0.0001, **p < 0.01, *p < 0.05. Source data are provided as a Source Data file