Plasma proteomes of acute myeloid leukemia patients treated with transfusions reveal signatures of inflammation and hemostatic dysregulation

Abstract

Abstract Background Bone marrow aplasia is a common feature in acute myeloid leukemia (AML) patients during their remission induction treatment, and is associated with potential complications such as bleeding, infection and anemia. Frequent platelet and red cell transfusions are administered to prevent and treat these complications. However, platelet counts are poorly associated with bleeding events in this population. Therefore, plasma protein levels could add valuable insights to improve our understanding of the patient's health state. In this study, we aimed to delineate the plasma proteome, including inflammatory pathways, hemostatic and immune components, of AML patients during treatment with intensive transfusion support. Methods We employed unbiased mass spectrometry (MS)-based proteomics on longitudinal plasma samples from 10 AML patients during intensive-transfusion treatment phase with healthy individuals as baseline control. Results A total of 450 proteins were quantified in plasma samples from AML patients and healthy controls. Alteration in proteins levels were mainly observed for proteins involved in inflammation (e.g. SAA1 and CRP), and complement (e.g. C9 and MASP2) when comparing AML versus healthy individuals. Correlation analysis revealed additional affected protein dynamics, including proteins associated with coagulation cascade, endopeptidase inhibitors activity and lipoprotein remodeling. Conclusion The plasma proteome from AML patients during intensive treatment shows a disbalance in inflammation, endopeptidase inhibitors activity, lipoprotein remodeling, coagulation and complement. These effects and potential associations with bleeding risk will be further studied in a bigger cohort.

Keywords

• Transfusion
• AML
• Proteomics
• Plasma profiling
• Platelets
• Red blood cells