Xenograft models of human DLBCL

SU-DHL-6, DOHH-2, OCI-LY8, or OCI-LY7 cells (10⁶) were transplanted subcutaneously in irradiated (3 gray) CD1-nude nu/nu female mice. Treatment started upon the appearance of measurable tumors. Tumor volumes were assessed from the start of the treatment every 2 days with a digital caliper and calculated as 1/2(length × width²) (66). The following treatment schemes were used: twice a day intraperitoneal injection of tigecycline (spaced by ~8 hours) and/or daily oral gavage with venetoclax for 5 days, followed by 2 days off and a repeat of the same scheme, for a total of 12 days. A single intravenous injection of rituximab (10 mg/kg) was used for the experiment in fig. S9. For the experiment in fig. S5 (B and C), tigecycline was delivered with a single intravenous injection every 3 days, for a total of 12 days. Tigecycline was dissolved in saline solution (0.8% NaCl); venetoclax was dissolved in 60% Phosal 50 PG (Lipoid), 30% polyethylene glycol (Sigma-Aldrich), and 10% ethanol. Solutions were freshly prepared from dry powder just before each injection.

The PDX line DFBL-69487-V3-mCLP (33) was acquired from the Public Repository of Xenografts (www.proxe.org). Cells (10⁶) were xenografted via tail vein injection into 6- to 8-week-old female NSG mice. The animals were monitored once a week by whole-body imaging on an IVIS Lumina III platform after intraperitoneal injection of XenoLight D-Luciferin (150 mg/kg) (#122799, PerkinElmer) and anesthesia with isoflurane. The data were analyzed with the Living Image software, version 4.2 (Caliper Life Sciences). Radiant efficiency was calculated on the basis of the epifluorescence signal, as indicated in the user manual. Experiments involving animals were carried out in accordance with the Italian Law D.lgs. 26/2014, which enforces Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.