HOPE

Myeloproliferative neoplasms (MPN) are genetically driven hematopoietic stem cell diseases. They are characterized by a huge symptom burden, increased risk of thrombosis and bleeding as well as of leukemic transformation. Several treatment options are currently available, but therapies are often inefficient or resistance to therapy develops. Thus, novel biomarkers guiding the choice between high and low-intensity treatment options balancing clinical response parameters with patient-reported outcomes including side-effects caused by toxicity to provide a truly person-centred precision medicine is urgently needed. The inclusion of multidimensional high-content -omics data provides an opportunity for developing powerful pharmacogenomic markers to guide treatment decisions. In this collaborative European project we will: 1. Build a unique cohort of MPN patients including longitudinal biological samples with both clinical information, patient reported outcomes (PROs) and high-content molecular proteogenomic data. 2. Identify pharmacogenomic markers by correlating multidimensional high-content data with clinical outcome and patient-reported symptoms also considering side effects in response to different treatment schemes. 3. Increase the resolution and biomarker discovery power by including longitudinal samples, ex vivo generated response signatures and single-cell resolution. As a side objective with potential high impact, we will test response-associated nodes as potential combinatorial drug targets. 4. Determine requirements for clinical implementation by addressing regulatory aspects, assessing technical feasibility, planning steps for technical transfer including a stakeholder and market analysis. This ambitious builds on established collaborations and strong preliminary data to form the HOPE consortium. We will combine the complementary expertise of clinicians, translational researchers, computational biologists, patient representatives and regulatory experts to generate biomarkers for a patient-centred therapy of MPN.