Gene expression profiles were examined in 33 adult patients with T-cell acute lymphocytic leukemia (T-ALL). Nonspecific filtering criteria identified 313 genes differentially expressed in the leukemic cells. Hierarchical clustering of samples identified 2 groups that reflected the degree of T-cell differentiation but was not associated with clinical outcome. Comparison between refractory patients and those who responded to induction chemotherapy identified a single gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells and a set of 30 genes that was highly expressed in leukemic cells from patients who achieved complete remission. We next identified 19 genes that were differentially expressed in T-ALL cells from patients who either had a relapse or remained in continuous complete remission. A model based on the expression of 3 of these genes was predictive of duration of remission. The 3-gene model was validated on a further set of T-ALL samples from 18 additional patients treated on the same clinical protocol. This study demonstrates that gene expression profiling can identify a limited number of genes that are predictive of response to induction therapy and remission duration in adult patients with T-ALL. (Blood. 2004;103:2771-2778)