Figure 2. . F10 displays strong antileukemic activity with minimal systemic toxicities.
(A) F10 confers a survival benefit equivalent to the combination of Ara-C and doxorubicin. C57/Bl6 mice were sublethally irradiated to 4.5 Gy and injected with an MLL-ENL and Flt3 ITD syngeneic AML. Once engraftment was established by bioluminescence imaging, mice were treated with either saline (control), F10 at 300 mg/kg (FdUMP [10]), 5-FU at 121 mg/kg (5-FU) or cytarabine at 125 mg/kg plus doxorubicin at 3.75 mg/kg (Ara-Dox) on days 1, 3, 5 and 7. (B) F10 is active against multiple ALL models in vivo. Survival of C57Bl/6 mice injected with syngeneic, Ph+ B-cell ALL model and treated with saline or F10 at 300 mg/kg every other day for 4, 6 or 9 doses as indicated. (C) Survival of ALL xenograft bearing mice from time of injection treated with saline or F10 at 300 mg/kg every other day ×5 doses as indicated. All p-values were derived from log-rank tests. (D–G) F10 (F) causes much less bone marrow toxicity than 5-FU (D) or AraC-Dox (E) – regions of hypocellularity are indicated with yellow arrows. Panel (G) is vehicle-treated control. Drug dosing was the same as in panel (A).
5-FU: 5-fluorouracil; ALL: Acute lymphocytic leukemia; AML: Acute myeloid leukemia.