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    Oral Communication

    Hemostatic Systems in Cancer, Inflammation and Immunity

    Hemostatic Mechanisms in Cancer and Autoimmunity

    OC 56.1 - Platelets as Versatile Effectors of Thromboinflammation: an MPN multi-omics collaborative

    Tuesday, June 27, 2023
    10:45 – 11:00 ET
    Room: 524
    Session Available As: On-Demand

      Presenting Author(s)

    • Sarah Kelliher, MB (she/her/hers)

      Clinical Research Fellow
      UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland, Dublin, Ireland

      • Co-Author(s)

    • SG

      Sara Gamba

      Researcher
      Department of Immunohematology and Transfusion Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy
      Bergamo, Lombardia, Italy

    • Luisa Weiss, BSc, MSc, PhD

      Post-doctoral Scientist
      School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
      Dublin, Dublin, Ireland

    • Marina Marchetti, PhD (she/her/hers)

      Hemostasis Lab Director
      Department of Immunohematology and Transfusion Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy
      Bergamo, Lombardia, Italy

    • FS

      Francesca Schieppati

      Hematologist
      Department of Immunohematology and Transfusion Medicine, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
      Bergamo, Lombardia, Italy

    • FN

      Fionnuala Ní Áinle

      Consultant Haematologist
      Department for Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
      Dublin, Dublin, Ireland

    • Patricia B. Maguire, PhD

      Full Professor
      School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
      Dublin, Dublin, Ireland

    • Anna Falanga, MD (she/her/hers)

      Professor of Hematology
      Department of Immunohematology and Transfusion Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy
      Bergamo, Lombardia, Italy

    • Barry Kevane, MB PhD

      Consultant Haematologist
      Mater Misericordiae University Hospital & University College Dublin
      Dublin, Dublin, Ireland

    • Anandi Krishnan, PhD

      Instructor
      Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
      Stanford, California, United States

    Background: Patients with Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) exhibit a tendency toward thrombosis and hemorrhage and clinical manifestations of microcirculatory disturbances. Although an increase in blood cell lineages contributes to these morbid sequelae, the qualitative abnormalities of myeloid cells that increase vascular risk are not well understood.

    Aims: Considering the critical role of inflammation in vascular risk, and the emerging evidence for platelet functional interplay between thrombosis, inflammation, and cancer, we evaluated the MPN platelet proteo-transcriptome at independent sites as part of a study approved for an ISTH fellowship.

    Methods: For platelet transcriptomics, blood samples from patients and controls (n=120) were obtained with consent and approval by the Stanford Institutional Review Board (IRB). Sequencing and analysis were performed at the Stanford Functional Genomics facility using the Illumina GAIIx sequencer. Downstream statistical analyses were performed with R, version 3.3.3. Following consent and IRB approval, samples for proteomic analysis from patients and controls (n=140) were obtained at Papa Giovanni XXIII Hospital, Bergamo, and the Mater Misericordiae University Hospital, Dublin. Platelet proteomic signatures were established by label-free quantification (LFQ) mass spectrometry (MS), using a Bruker TimsTOF mass spectrometer with a EvoSep liquid chromatography system. Identified peptides were searched using MaxQuant. Differences in protein expression were determined using Perseus.

    Results: Using platelet transcriptomic and proteomic data derived at independent sites of MPN patient recruitment, we identify 152 significant candidate genes (FDR < 0.05) at both RNA and protein levels as potential mediators of the pro-thrombotic phenotypes in MPN. Markers identified both confirm previously established genes (e.g. protein disulfide isomerase PDIA4, Fc gamma receptor, FCGR2A) as well as offer new candidates for further validation (e.g. coatomer complex golgi transport COPB2 and threonyl tRNA synthetase TARS).

    Conclusion(s): Our findings from this multi-site study indicate a novel role for the platelet molecular profile in offering a unique, peripherally accessible window into MPN thromboinflammation.

    Learning Objectives:

    • Discuss the heterogenous and versatile role of platelets in cancer.
    • Describe the platelet proteomic and transcriptomic signatures in patients with MPN.
    • Recognise the platelet molecular profile as a novel mediator of thromboinflammation in MPN.