Figure 6.
Stabilized SNAI1 through acetylation determines the fate of giant cells. (A) Western blots showing the protein levels of SNAI1 in response to PBN treatment for 72 hours and ACLi for 48 hours. (B) Immunofluorescence assay showing the presence of giant cells are indicated by selectively increased levels of SNAI1 in a PDO sample (PT6) treated with or without PBN ex vivo. Arrows indicate the presence of giant cells. Blue, DAPI; red, SNAI1 (Texas red). Scale bar, 100 μm. (C) Western blots of CD19 and SNAI1 in giant cells treated with ACLi and supplemented acetate (48 hours). (D) Western blots showing Dox-inducible expression of FLAG-tagged ACL in Acly-knockdown cells (Dox, 1 μg/mL for 72 hours). (E) Representative spheroid 3D culture (2 weeks) of Acly- or Snai1-knockdown giant cells and Acly-knockdown giant cells with or without Dox-inducible ACL expression. Acetate, 20 mM. (F) Western blots of SNAI1 and CD19 levels in tumors from patients with MCL with increased therapeutic stress. (G) Western blots of SNAI1 and CD19 levels in tumors from patients with MCL sensitive to BTKis (BTKi-S), resistant to BTKis (BTKi-R), and resistant to BTKi and CAR T-cell therapy (BTKi-R/CAR-T-R). Ctrl, control; Dox, doxycycline; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

Stabilized SNAI1 through acetylation determines the fate of giant cells. (A) Western blots showing the protein levels of SNAI1 in response to PBN treatment for 72 hours and ACLi for 48 hours. (B) Immunofluorescence assay showing the presence of giant cells are indicated by selectively increased levels of SNAI1 in a PDO sample (PT6) treated with or without PBN ex vivo. Arrows indicate the presence of giant cells. Blue, DAPI; red, SNAI1 (Texas red). Scale bar, 100 μm. (C) Western blots of CD19 and SNAI1 in giant cells treated with ACLi and supplemented acetate (48 hours). (D) Western blots showing Dox-inducible expression of FLAG-tagged ACL in Acly-knockdown cells (Dox, 1 μg/mL for 72 hours). (E) Representative spheroid 3D culture (2 weeks) of Acly- or Snai1-knockdown giant cells and Acly-knockdown giant cells with or without Dox-inducible ACL expression. Acetate, 20 mM. (F) Western blots of SNAI1 and CD19 levels in tumors from patients with MCL with increased therapeutic stress. (G) Western blots of SNAI1 and CD19 levels in tumors from patients with MCL sensitive to BTKis (BTKi-S), resistant to BTKis (BTKi-R), and resistant to BTKi and CAR T-cell therapy (BTKi-R/CAR-T-R). Ctrl, control; Dox, doxycycline; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal