Fig 6.

Mutant SEC61A1 is directly responsible for ER stress and a genotype-specific arrest in neutrophilic differentiation. A, Mean percentage of undifferentiated, CD11b⁺CD16^–, and CD11b⁺CD16⁺ HL-60 cells stably transduced as indicated on day 6 (D6) of differentiation by using 1% DMSO (n = 7). B, Percentage of CD11b⁺CD16⁺ HL-60 cells from (A) gated on live, GFP⁺ cells on day 6 of differentiation (n = 7). C, Mean fluorescence index (MFI) of CD16 on CD16⁺ HL-60 cells gated on live GFP⁺ cells on day 6 of differentiation (n = 7). Paired t test. D, MFI of CD16 on CD16⁺ neutrophils isolated from whole blood or bone marrow (BM) from the HC and P normalized to WT MFI within each independent repeat. E, Quantification of hematoxylin and eosin (H&E) staining of untreated and 1% DMSO-treated stably transduced HL-60 cells for 6 days from representative repeat in (A). F, Representative H&E staining from differentiation in (A-C). The symbol # indicates promyelocyte-like, the symbol < means myelocyte-like, the symbol % means metamyelocyte-like, and the symbol ∗ means terminally differentiated cell. G, mRNA expression of DDIT3 (CHOP [left]) and HSPA5 (BiP [right]) normalized to 18S in transduced HL-60 cells left untreated or treated with 1 μM thapsigargin for 24 hours. Each fold change represents treated over average of untreated (n = 8). Unpaired t test.