Page 114 - Haematologica Vol. 110 - January 2025

ARTICLE - LIPA modulates venetoclax/TKI response in bpCML M. Minhajuddin et al. AB
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Figure 1. The venetoclax/dasatinib combination targets bulk cells and the leukemia stem cell compartment in a mouse model of blast phase chronic myeloid leukemia. (A, B) Viability of bulk cells (A) and the leukemia stem cell (B) compartment (Lin–Sca1+) of GY leukemia cells treated in vitro with venetoclax (100 nM), dasatinib (100 nM), or their combination after 24 hours compared to cells treated with the vehicle control. (C, D) Leukemic mice were treated with vehicle, venetoclax alone (100 mg/kg/day, oral ga- vage), dasatinib alone (20mg/kg/day, oral gavage) and the combination for 5 days starting at day 7 after transplantation of leuke- mic cells. Mice were sacrificed at day 12 after the transplantation and the tissues were harvested to determine bulk (C) and leukemic stem cell (D) leukemic burden in bone marrow. (E) Leukemic mice were treated with vehicle, venetoclax alone, dasat- inib alone and the combination, as described above. Survival of control and treated leukemic mice (N=8) was monitored and mice were sacrificed upon demonstration of morbid symptoms. No such symptoms appeared in mice treated with the combination, so these mice were sacrificed 80 days after the start of the experiment. (F) Representative flow plot for engraftment status of leukemia cells (GY cells) from the survival experiment illustrated in (E). **P≤0.01, ***P≤0.001. Ven/Dasa: venetoclax and dasatinib combination; LSC: leukemia stem cells; WT: wild-type; Ven: venetoclax; Dasa: dasatinib.
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