SOX11 sensitizes MCL to ara-C treatment in vivo and HU mimics SOX11-mediated sensitization to ara-C in SOX11⁻ MCL cell lines. (A) Kaplan-Meier analysis of NOD/SCID mice injected with JVM-2^vector or JVM-2^iSOX11 that received ara-C (100 mg/kg) after 5 days of injection with cells vs untreated controls; n = 8 per group. (B) Immunohistochemistry revealing SOX11 and SAMHD1 staining in formalin-fixed paraffin-embedded (FFPE) tumor tissue from mice injected with either JVM-2^vector or JVM-2^iSOX11 treated with doxycycline; scale bar, 50 μm. (C-D) Dose response curves for cytarabine when combined to the indicated concentrations of HU (on the right side of the curves) in JVM-2^vector and JVM-2^iSOX11, respectively. Cells were treated with 0.1 μM doxycycline for 24 hours before combined treatment with ara-C and HU, which lasted for 72 hours until viability was measured using the CellTiter-Glo Luminescent Cell Viability Assay. Data of 3 independent experiments are represented as mean ± SEM. (E) Western blot analysis of apoptosis and DNA damage markers upon single treatment of ara-C (0.5 μM) or HU (50 μM) or their combination vs the respective untreated controls in JVM-2^vector and JVM-2^iSOX11. After 24 hours of 0.1 μM doxycycline treatment, combined or single treatments were performed for 24 hours. The blot is a representative out of 3 independent biological replicates. Protein sizes: cleaved PARP1 (89 kDa), SOX11 (74 kDa), SAMHD1 (71 kDa), phospho-ChK2 (T68) (∼62 kDa), GAPDH (37 kDa), cleaved caspase-3 (17 kDa), and γ-H2A.X (14 kDa).