Early response evaluation by single cell signaling profiling in acute myeloid leukemia

Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, we find that reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24h post-chemotherapy is a significant predictor of patient 5-year overall survival in this cohort. Validation by RNA sequencing show induction of MAPK target gene expression in patients with high phospho-ERK1/2 24h post-chemotherapy, while proteomics confirms an increase of the p38 prime target MAPK activated protein kinase 2 (MAPKAPK2). In this study, we demonstrate that mass cytometry can be a valuable tool for early response evaluation in AML and elucidate the potential of functional signaling analyses in precision oncology diagnostics. In this study we investigate the singlaing response to standard induction therapy in a cohort of 32 acute myeloid leukemia (AML) patients. Samples were taken at pre-treatment (0h), 4 hours and 24 hours after start of chemotherapy. We validated our results by proteomics and RNA-sequencing. RNA sequencing was performed for some of these patients at all tiempoints available.