Figure 6.
Figure 6. In vitro sensitivity of T-ALL to dasatinib correlates with antileukemic efficacy in the patient. (A) Subset of T-ALL patients at diagnosis that relapsed (R) and at relapse are highly sensitive to dasatinib in vitro. (B) Dasatinib-sensitive T-ALL cells have higher levels of phosphorylated SRC that decreases after treatment with 1 µM dasatinib for 2 hours as measured by flow cytometry. (C) Dasatinib response correlates with sensitivity to the SRC inhibitor KX2-391 (n = 16). (D) In vitro captured response correlates with in vivo response to dasatinib (n = 10). Indicated is the percent of T-ALL blasts compared with mouse lymphocytes normalized to vehicle-treated controls. (E) Sensitivity of adult and pediatric T-ALL patients to dasatinib reveals 40% of patients with IC50 below 100 nM. (F) Left: positron emission tomography/computed tomography (PET/CT) scan demonstrates significant disease burden throughout the marrow in bilateral upper and lower extremities, the pelvis, vertebrae, and contiguous nodes within the mediastinum. Right: PET/CT ∼15 months after the original presentation, shortly after initiation of dasatinib monotherapy. This image demonstrates complete response (CR) with no signs of marrow or nodal involvement. *P = .0272; **P = .0072; ***P = .0004; ****P = .0001. BM, bone marrow; PB, peripheral blood; SP, spleen.

In vitro sensitivity of T-ALL to dasatinib correlates with antileukemic efficacy in the patient. (A) Subset of T-ALL patients at diagnosis that relapsed (R) and at relapse are highly sensitive to dasatinib in vitro. (B) Dasatinib-sensitive T-ALL cells have higher levels of phosphorylated SRC that decreases after treatment with 1 µM dasatinib for 2 hours as measured by flow cytometry. (C) Dasatinib response correlates with sensitivity to the SRC inhibitor KX2-391 (n = 16). (D) In vitro captured response correlates with in vivo response to dasatinib (n = 10). Indicated is the percent of T-ALL blasts compared with mouse lymphocytes normalized to vehicle-treated controls. (E) Sensitivity of adult and pediatric T-ALL patients to dasatinib reveals 40% of patients with IC50 below 100 nM. (F) Left: positron emission tomography/computed tomography (PET/CT) scan demonstrates significant disease burden throughout the marrow in bilateral upper and lower extremities, the pelvis, vertebrae, and contiguous nodes within the mediastinum. Right: PET/CT ∼15 months after the original presentation, shortly after initiation of dasatinib monotherapy. This image demonstrates complete response (CR) with no signs of marrow or nodal involvement. *P = .0272; **P = .0072; ***P = .0004; ****P = .0001. BM, bone marrow; PB, peripheral blood; SP, spleen.

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