SRP409520 PRJNA904775 GSE218664 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. Overall design: 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. GSE218664 pubmed 36611026