A quantitative analysis of heterogeneities and hallmarks in acute myelogenous leukaemia

Acute myelogenous leukaemia(AML) is associated with risk factors that are largely unknown and with a heterogeneous response to treatment. Here, we provide a comprehensive quantitative understanding of AML proteomicheterogeneities and hallmarks by using the AML ProteomeAtlas, a proteomicsdatabase that we have newly derived from MetaGalaxy analyses, for the proteomicprofiling of 205 patients with AML and 111 leukaemia cell lines. The analysis of the dataset revealed 154 functional patterns based on common molecular pathways, 11 constellations of correlated functional patterns and 13 signatures that stratify the outcomes of patients. We find limited overlap between proteomicsdata and both cytogenetics and genetic mutations. Moreover, leukaemia cell lines show limited proteomicsimilarities with cells from patients with AML, suggesting that a deeper focus on patient-derived samples is needed to gain disease-relevant insights. The AML ProteomeAtlas provides a knowledge base for proteomicpatterns in AML, a guide to leukaemia cell line selection, and a broadly applicable computational approach for quantifying the heterogeneities of protein expression and proteomichallmarks in AML.