Differential activation of basal and IL-7-induced PI3K/Akt/ mTOR and JAK/STAT5 signaling distinguishes pediatric from adult acute lymphoblastic leukemia

The age distribution of cases of B-cell acute lymphoblastic leukemia (B-ALL) is bimodal, peaking in childhood at 2-5 years of age and in adults after the age of 50, with children displaying significantly better prognosis than adults. Signaling pathways triggered by leukemia cell-autonomous lesions or by extracellular cues, such as interleukin-7 (IL-7), have been shown to play a pivotal role in B-ALL biology and response to treatment.1-3 However, whether age-related differences exist in signaling pathway activation between pediatric and adult cases of B-ALL has not been scrutinized. Here, we characterized the basal and IL-7-induced PI3K/Akt/ mTOR and JAK/STAT5 signaling profile of pediatric patients age (range, 1-14 years) and adult patients age, (range, 29-75 years), using phospho-specific flow cytometry. We show that there are clear age-related differences in signaling activation that correlate with sensitivity to pathway-specific small molecule inhibitors. Our results underline the importance of considering the age group when predicting potential clinical benefits of signaling targeted therapies.