Signaling changes in the stem cell factor–AKT-S6 pathway in diagnostic AML samples are associated with disease relapse

Although current chemotherapy regimens are effective at eliminating the bulk of acute myeloid leukemia (AML) blasts, the disease relapses in the majority of patients. Whether relapse arises through the selection of a relatively rare subpopulation of cells present at diagnosis having specific characteristics that facilitate chemoresistance or through the induction of changes required to render them resistant to the chemotherapy is uncertain. Identification of the characteristics that confer chemoresistance, whether selected or induced, would allow for the implementation of additional therapies that target the lynchpin of resistance, thus improving disease outcome. This study evaluated whether single-cell network profiling (SCNP), a process that simultaneously measures post-translational protein modifications (for example, phosphorylation, acetylation and so on) in multiple signaling pathways within a single cell, could be used to functionally characterize intracellular pathways associated with in vivo AML chemotherapy resistance. Specifically, we hypothesized that leukemic blasts at relapse have different signaling characteristics from those at diagnosis and that assessing intracellular signaling networks