Single-cell Phospho-Profiling in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Reveals Signaling Differences in Cytogenetic and Prognostic Subgroups
Reasons for poor response to therapy and/or relapse in pediatric ALL remain poorly understood, especially in patients originally stratified into low-risk groups. As it is widely known that oncogenesis and tumor progression are supported by alterations in cellular signaling, we analyzed 22 primary xenografted BCP- ALL samples in respect to their potential to react to a given stimulus in vitro and related the phosphorylation profiles to the clinical characteristics of the corresponding patients. Phospho-specific antibodies in combination with surface staining in flow cytometry were used to analyze specific signaling molecules of leukemia cells at a single cell level.
We detected differences in signaling patterns between cytogenetic subgroups as well as other prognostic subgroups (e.g. CD34-positivity, hyperleucocytosis, response to induction chemotherapy and relapse).
Despite similar basal phosphorylation levels, cytogenetic and other prognostic subgroups display specific profiles of signaling networks after stimulation with various stimulants. This strategy will therefore prove helpful to identify mechanisms by which different subgroups with distinct clinical outcomes interpret environmental signals and hereby define pathways important for continued survival, proliferation and resistance eventually leading to novel biomarkers and targeted therapies.