TFEB is a mediator of apilimod sensitivity in B-NHL. (A) Heat map representation of gene expression changes in SU-DHL-10 and WSU-DLCL2 B-NHL lines treated with 300 nM apilimod for 24 hours. Red color represents upregulated genes; blue color represents downregulated genes. (B) GO analysis of commonly upregulated genes from panel A reveals an enrichment for lysosomal-associated genes. (C) LysoTracker staining in SU-DHL-6 and SU-DHL-10 for 24 and 48 hours after treatment with 200 nM (blue) apilimod compared with DMSO-treated control (red). (D) Nuclear and cytoplasmic levels of TFEB protein assayed by immunoblotting in SU-DHL-6 cells treated with apilimod (63 nM) for 2 hours. A representative blot is shown from 2 independent experiments. (E) Stable CA46 (TFEB-deficient B-NHL) pools overexpressing either GFP control or TFEB were treated with 10-point apilimod dose response for 3 days. Data are represented as mean ± SD. (F) Box plots showing relative TFEB messenger RNA (mRNA) levels across tumor types, extracted from CCLE³⁵  with gene-centric robust multiarray analysis-normalized mRNA expression data. “Lymphoma Other” includes B-cell lymphoma unspecified (8), anaplastic large-cell lymphoma (5), chronic lymphocytic leukemia–small lymphocytic lymphoma (5), mantle cell lymphoma (4), mycosis fungoides–Sezary syndrome (3), peripheral T-cell lymphoma unspecified (1), T-cell large granular lymphocytic leukemia (1), and unclassified (1). B-NHL cell lines are highlighted with a red box. ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; LOG2FC, LOG2 fold change; mRNA, messenger RNA; NSC, non-small cell; RMA, robust multiarray average.