Mass spectrometry-based techniques now enable the unbiased identification of proteins in complex mixtures including proteins isolated from cells and tissues. These powerful tools permit near-complete annotation of proteins expressed in cells, tissues or organs. Further, these techniques permit the interrogation of the numerous post translational modifications that govern cell-specific responses to signaling cues and underlie the functional heterogeneity of cellular composition and contribute to biological complexity. Parallel developments in technologies such as mass cytometry and multicolor ion-beam imaging which permit multi-parameter detection of numerous proteins at the single cell and in-situ level respectively are poised to radically impact our understanding of the functional and translational importance of proteins in hematologic conditions. Importantly, the field of proteomics is poised to realize the immensely powerful opportunities in integration with genomic information that is being discovered at an unprecedented pace for many hematologic conditions.

Introduction

Over the last 20 years, the relationship between cellular genotype and phenotype has been interrogated based on the assumption that there is a direct link between gene and protein function. Technologies to interrogate the genome at global scale such as whole genome sequencing (WGS), whole exome sequencing (WES) or RNA-sequencing (RNA-Seq) are in wide use. However, with the exception of few single gene defects, most disease phenotypes are more complex and remain largely unknown. Although proteins are the effectors of the cell’s genetic code many studies have demonstrated a poor correlation between mRNA and protein expression level [1, 2]. Thus, while recent advances in WGS, WES and RNA-Seq have made unparalleled discoveries in the field of hematology and hematologic malignancies, there remains a critical need for methods to analyze proteins and their functions in a high throughput and largescale manner. Mass spectrometry (MS) and in particular tandem mass spectrometry (MS/MS) allows simultaneous identification and quantification of thousands of proteins in complex biological samples. Accordingly MS-based proteomic approaches permit the identification of disease biomarkers, protein-protein interactions involved in signaling and post-translational modifications such as phosphorylation and N-glycosylation which are critical events in a variety of hematologic disorders. In this review, we will discuss basic principles of MS-based proteomics and their applications in a variety of hematologic disease. Figure 1 summarizes the specimens, components and selected approaches encompassed by proteomics.