In vivo antitumor activity of APO866 in mouse xenograft models of human leukemia and lymphoma. (A) In vivo efficacy of APO866 on mice xenografted with ML-2 cells. Fifteen 6- to 8-week-old Balb/c nude mice received subcutaneous transplants of 2 × 10⁷ ML-2 cells. Once tumors became palpable (approximately 150 mm³, at day 18), mice were randomized into a control group (n = 7, black line) and a treated group (n = 8, colored line). APO866 administration and tumor volume assessment were conducted as described in “Methods.” (B)Treatment with APO866 at early stage of disease prevents tumor growth and prolongs survival in a mouse model of human Burkitt lymphoma. Twenty 6- to 8-week-old C.B.-17 SCID mice were each injected subcutaneously with 10⁷ Namalwa cells and mice were subdivided into 2 groups. APO866 administration was initiated as described in “Methods” starting 1 week after cell injection (n = 10), whereas mice in the control group (n = 10) received intraperitoneal injection with saline solution. (C) APO866 applied on established human Burkitt lymphoma tumors abrogates tumor growth. Mice underwent transplantation with Namalwa cells as described in panel B. When tumors reached a volume of 100 mm³ (at day 14), mice were divided in 2 groups. Mice from APO866 group were treated with APO866 as described above (n = 10) and control animals (n = 10) received vehicle only. (D) APO866 treatment eradicates tumor growth and prolongs the overall survival in a mouse model of human Burkitt leukemia. Raji-GFP cells (5 × 10⁴) were injected into the tail vein of each SCID mouse (D0). Starting 1 week after cell injection, animals were treated with APO866 (n = 10, colored line) or received vehicle (n = 8, black line). All animals were monitored daily, and the end point of the study was survival defined as the time point where hind limb paresis was noted. Animals that reached end point or survived after 180 days of observation were killed. ***P < .001. (E) Detection of t(8;14)(q24;q32) DNA fragment specific of Raji cells (Burkitt lymphoma). DNA was extracted from 17 bone marrow cells from either vehicle-injected (lanes 2-9) or APO866-treated mice (lanes 10-18). Positive and negative controls for PCR included DNA from pure Raji cells (lane 1) and buffer (lane 19), respectively. M: DNA ladder mix marker (Fermentas Life Science, Madison, WI).