Proteomic approaches for untangling pharmacological targets in acute myelogenous leukemia

Acute myelogenous leukemia (AML) is a highly malignant disease of the blood and bone marrow [1]. A block in differentiation in normal hematopoiesis leads to accumulation of immature cells that compromise normal bone marrow function, resulting in severe bone marrow failure [1]. The disease has a highly malignant and aggressive course, and without treatment, the disease will usually be fatal within weeks to months. In contrast to breakthroughs in treating other cancers, the progress of therapy in AML has been slow overall, although new drugs have recently entered the field [2]. Furthermore, AML represents a various disease spectrum, reflected by a myriad of cytogenetic abnormalities and genetic mutations. Although well recognized and highly predictive, they do not fully capture the degree of heterogeneities manifested clinically. Disease heterogeneity resulting from variability in leukemic cell maturation state, a large diversity of genetic aberrations among patients, and the existence of multiple disease clones within a single patient have been extensively characterized. However, despite the extensive adoption of genomic approaches in cancer research, it is widely recognized that genomics alone is insufficient to provide an accurate picture of all cellular changes and dynamic states. In contrast, mass spectrometry (MS)-based proteomics has the potential to untangle the intracellular specter of intracellular proteins and hence complement limitations of genomic approaches, advancing the discovery of a potential therapeutic and druggable protein for improving personalized treatments in AML.