(A) Stromal (HK) cells support lymphoma formation in vivo. HBL-2 cells (1 × 10⁶ cells) were subcutaneously injected with or without HK cells (5 × 10⁵ cells) into the posterior flank of NOD/SCID mice. The graph shows tumor size measured at the indicated days after cell injection. Photographed tumors inoculated by HBL-2 alone or HBL-2 coinoculated with HK (HBL-2+HK) on day 26 are also shown. *P < 0.05. (B) Enforced expression of miR-548m suppressed lymphoma formation. HBL-2 cells were transfected with pre-miR control (pre-miR-Ctrl) or pre–miR-548m for 24 hours and injected without and with HK cells. *P < 0.05. (C) Treatment with tubastatin A significantly inhibited tumor growth in the absence and presence of HK cells. *P < 0.05. (D) Treatment with tubastatin A enhanced mitoxantrone-induced lymphoma killing in vivo in NOD/SCID mice bearing HBL-2 xenografts. (B–D) NOD/SCID mice were inoculated subcutaneously in the right flank with 1 × 10⁶ HBL-2 cells with and without HK cells (5 × 10⁵ cells). Two weeks later, when palpable tumors (≥5 mm in diameter) developed, mice were treated with intraperitoneal injections of (C) tubastatin A alone (25 mg/kg/d) for 14 consecutive days or (D) mitoxantrone alone (1.5 mg/kg/d) on days 1, 2, 3, 4, 8, 9 10, and 11 or the tubastatin A–mitoxantrone combination for 14 consecutive days. Each group consisted of 4 to 6 mice. *P < 0.05, significantly delayed tumor growth. The inset shows a typical representative of each treatment group. Data are shown with mean ± SD.