Impact of SURF4 on myeloid leukemic cells. (A) SURF4 shRNA‐mediated THP1, HL60, and K562 cells were counted every two days. (B) Quantification of apoptotic cells from SURF4 shRNA‐mediated THP1, HL60, and K562 cells. (C) Tumorigenicity was analyzed with a xenograft model of NOD‐SCID mice. Subcutaneous injection of SURF4 shRNA‐mediated HL60 cells was performed and tumor growth was quantified (n = 5). (D‐F) Quantification of the apoptotic cells from SURF4 shRNA‐mediated THP1, HL60, and K562 cells after paclitaxel (D), cytarabine (E), or tunicamycin (F) treatment. (G) Quantification of the apoptotic cells from SURF4 shRNA‐mediated THP1 and HL60 cells after IL4 treatment. (H) Quantification of the apoptotic cells from SURF4 shRNA‐mediated THP1 cells after cGAMP treatment. (I) Quantification of the normalized fold change in MFI for the indicated phospho‐protein in SURF4 shRNA‐mediated THP1 cells. (J) Survival analyses for SURF4. Overall survival for 4 years with Kaplan‐Meier curve stratified by SURF4 expression. (K) UMAP visualization of cells from normal and AML patients. In the UMAP plot, each point represents a cell, and the space of the point reflects the location of the cell in low‐dimensional space based on transcriptional similarity. The left panel is colored by the cell type of bone marrow, and the right panel shows UMAPs separated by donor origin. (L) Gene expression levels of SURF4 in whole cells, progenitors, and HSCs. The Y‐axis of the violin plot is log‐normalized counts of SURF4, and the described p‐value was derived using the Wilcox rank‐sum test comparing the gene expression levels in the normal and AML cells. (M) SURF4 negatively regulates STAT6 and STING functions and suppresses differentiation and cell death in myeloid leukemic cells. Error bars indicated the S.E.M. (**** P ≤ 0.001, *** P ≤ 0.001, ** P ≤ 0.01, * P ≤ 0.05). (n = 2 independent experiments and 3 total measurements per group and treatment).
Abbreviations: ROS, Reactive oxygen species; ER, endoplasmic reticulum; STING, stimulator of interferon genes; STAT6, signal transducer and activator of transcription 6; SURF4, surfeit 4; sgRNA, single‐guide RNA; AML, acute myeloid leukemia; scRNA‐seq, single‐cell RNA sequencing; UMAP, uniform manifold approximation and projection; cDCs, conventional dendritic cells; GO, Gene Ontology.