A New Approach for the Diagnosis of Myelodysplastic Syndrome Subtypes Based on Protein Interaction Analysis

Leona Chrastinová,Kristýna Pimková,Jan E Dyr,Markéta Bocková,Pavel Šácha,Nicholas S Lynn,Alžběta Hlaváčková,Roman Kotlín,Jiří Suttnar,Jana Štikarová,Jaroslav Čermák,Ondřej Pastva,Martin Hubálek,Jiří Homola

doi:10.1038/s41598-019-49084-2

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies with a high risk of transformation to acute myeloid leukemia (AML). MDS are associated with posttranslational modifications of proteins and variations in the protein expression levels. In this work, we present a novel interactomic diagnostic method based on both protein array and surface plasmon resonance biosensor technology, which enables monitoring of protein-protein interactions in a label-free manner. In contrast to conventional methods based on the detection of individual biomarkers, our presented method relies on measuring interactions between arrays of selected proteins and patient plasma. We apply this method to plasma samples obtained from MDS and AML patients, as well as healthy donors, and demonstrate that even a small protein array comprising six selected proteins allows the method to discriminate among different MDS subtypes and healthy donors.

Highlights

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies that affect pluripotent hematopoietic stem cells[1]
This assay combines a protein chip, comprised of selected proteins having the potential to interact with blood plasma, with a Surface plasmon resonance (SPR) biosensor, which allows the observation of these interactions in a realtime and label-free manner
Four proteins were selected based on literature data, where studies of MDS serum[21] and proteomic studies of MDS plasma[22] have revealed intracellular adhesion molecule 1 (ICAM), vascular cell adhesion protein 1 (VCAM), alpha-2-HS-glycoprotein, and leucine-rich alpha-2-glycoprotein (LRG) as promising candidates

Summary

Introduction

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies that affect pluripotent hematopoietic stem cells[1]. Surface plasmon resonance (SPR) is an optical method that enables monitoring of biomolecular interactions and quantification of biomolecules in a label-free manner[14] Since their introduction in the 1990s, numerous SPR biosensor platforms have been developed for use in a variety of biomolecular applications; among these, SPR imaging (SPRi) biosensors allow for the parallelized observation of biomolecular interactions, increasing the throughput of SPR biosensor technology[15]. SPR biosensor technologies have been increasingly applied to the detection of biomolecules related to medical diagnosis[16] These current diagnostic methods to monitor specific protein concentrations represent a powerful and useful technology (both label-based and label-free), they require prior knowledge of the proteins being www.nature.com/scientificreports/. This is especially problematic for diseases (such as oncohematological diseases) having molecular bases that are not fully understood

Methods

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Discussion

Conclusion