Sensitivity of BCP ALL cells to inhibitors of pre-BCR signaling. A, Ten
cell lines (four pre-BCR-negative ALL, three pre-BCR-positive non-MEF2D-ALL, and three
MEF2D-ALL lines) were exposed to indicated inhibitors and their sensitivity with
respect to growth inhibition was tested. Cells were treated with varying
concentrations of the inhibitors as indicated for 3 days. Cell growth is shown
relative to that of vehicle-treated control cells (means ± SDs; n =
3). B, Two clinical MEF2D-ALL cell lines were analyzed as in
A. C, Immunodeficient mice were transplanted with Kasumi-7
cells engineered to express luciferase, which was monitored by bioluminescence imaging
(left). Ibrutinib, dasatinib, and vehicle controls were administered daily from day 1
to day 35 days after transplantation. The survival outcomes were also estimated using
the log-rank test (right). Both drugs reduced the leukemia burden and significantly
prolonged the survival duration (n = 5 for ibrutinib treatment,
otherwise n = 4).