Response to targeted treatments in myeloid leukemia can be highly variable despite similar morphologic and phenotype features of leukemia cells, in part due to the resistant stem cell component and immune response to the tumor cells. Deciphering the treatment resistant cells for their survival mechanisms is a disruptive in cancer diagnostics. Current flow cytometry tests lack the capacity to evaluate cell-specific signaling characteristics. Analysis of activated signaling cascades enables detection of activated cell types, whether they are cancer cells or immune cells comprising the tumor microenvironment. Tests for genetic mutations and gene expression levels mask the underlying cellular heterogeneity and cellular processes that are the cause of variability in treatment response. Thus, SCALPEL is a revolutionary new approach to derive cell types relevant to a given disease state based on key cellular processes such as signaling activation profiles.
The prototypic data are in chronic myeloid leukemia (CML), a cancer of blood cells exceptionally susceptible to treatment with targeted tyrosine kinase inhibitors. Certain activated cell types including progenitor and immune cells in CML could represent novel cell-based biomarkers with predictive relevance. SCALPEL can be applied to identify these cell types based on not only surface lineage markers but also signaling activation profiles. Differentially expressed and activated proteins represent attributes that can predict response to treatment and recurrence upon treatment discontinuation.