Figure 2.
Dasatinib-sensitive subgroup of T-ALL samples. (a) Drug sensitivity scores (DSS) of dasatinib in a cohort of 22 patient samples. These DSS values are calculated from growth inhibition measurements after 72 h of treatment in a 10-fold dasatinib dilution series (0.1–1000 nM), and a DSS value of 10 was used as the threshold for dasatinib sensitivity. (b) The expression of the T-ALL subtype defining transcription factor TAL1 in T-ALL patient samples and cell lines measured by RT-qPCR. The threshold for ectopic TAL1 expression (dashed line) is defined by the expression of TAL1 in SIL-TAL1 fusion-positive cell lines, indicated with black columns, and the striped columns represent the dasatinib-sensitive samples.17 Patient sample 4 was processed in a separate RT-qPCR batch. (c) The heat map of LCK, FYN, MAP2K5, MAP4K5, ABL1 and LYN expression in a separate GEO-based T-ALL sample data set (n=385). Samples are clustered based on the expression of T-ALL subtype-defining transcription factors: TAL1 (n=61+103), NKX2-1 (n=18), TLX1 (n=33), TLX3 (n=51), HOXA (n=56) and LYL (n=63). (d) LCK expression in T-ALL subtype clusters. The difference between TAL1 clusters and any other cluster was statistically significant (P<0.001, Mann–Whitney U-test).