Systematic development of combination chemotherapies has significantly improved the prognosis of acute lymphoblastic leukemia (ALL). Patients with T-cell ALL (T-ALL) still have less favorable outcomes, and the prognosis of relapsed T-ALL is dismal. 1 In order to find novel targeted therapies for T-ALL, we retrieved the gene expression profiles of 4430 leukemia samples from the Gene Expression Omnibus (GEO) and performed an in silico drug target screening, where the expression profiles were compared with known drug targets in the Drug signature database (DsigDB). 2, 3 This compound library contains both FDA (Food and Drug Administration)–approved and novel investigational drugs. Strong expression of Src family tyrosine kinase LCK was detected in T-ALL samples, exceeding that of other leukemias and normal T cells (Figure 1a), whereas a LCK-targeting drug, dasatinib, decreased the kinase activity of LCK to 1% in comparison with the control at a 100 nM concentration. 4 Dasatinib is known to have multiple intracellular targets, and we noticed that some of them had a similarly elevated expression in T-ALL patients (Figure 1b and Supplementary Figure S1). Therefore, our combinatorial drug/target screening suggests dasatinib as a candidate targeted therapy for T-ALL patients. To experimentally evaluate the potency of dasatinib, we treated T-ALL cell lines with increasing concentrations of dasatinib (1–1000 nM). After 72 h, the most significant response was seen in