Anaemia is the most common pathological condition affecting 1.6 billion individuals worldwide. It thus presents a serious health care problem and an economic burden. Reduction in red blood cell (RBC) number can be caused by blood loss, diet, stress conditions including endurance sport, and pathologies which are caused by primary genetic aberrations or are secondary to the malfunction of other cell types. Transfusion of RBC, which is often the only cure for severe cases of anaemia, is associated with risks such as thrombosis and transfusion reactions due to allo-immunisation. There is an unmet need to improve treatment of anaemia through early and accurate diagnosis, targeted treatment, and increased safety and effectiveness of RBC transfusion. The aim of RELEVANCE is to improve fast and cost-effective diagnosis of the underlying cause of primary anaemia, and to improve treatment options for both general and personalised medicine. We defined five key objectives: (1) to improve diagnostics of anaemia, particularly for hereditary rare forms of anaemia (RA); (2) to find novel treatments for anaemia that target RBC production, ageing and clearance; (3) to reduce premature loss of RBC following transfusion; (4) to produce cultured RBC for transfusion; (5) to monitor and optimise RBC function during sport and exercise. RELEVANCE will train 15 early stage researchers (ESR) at four SMEs and eight academic partners, two of whom are at blood supply centres and two are diagnostic centres for RA. The continuous interactions between the clinic, blood supply centers, basic research, and industry will select for the most relevant unmet medical needs, and will stimulate innovative procedures that are immediately probed for applicability and validity both in a research and a clinical setting. RELEVANCE will organize three open access summer schools, extending training beyond the ESR of the ITN sustaining the critical number of young talented professionals in the field.

CarrerasLeaders is a new innovative and international postdoctoral programme, designed by Josep Carreras Leukaemia Research Institute (IJC), an independent, non-profit biomedical research institute that is part of the Government of Catalonia network of Research Centres (CERCA). IJC is the first European institute exclusively devoted to leukaemia and other malignant blood diseases. The aim of the programme is to fund 16 excellent postdoctoral researchers for a period of 36 months. The selection of the fellows is merit-based, founded on peer review in an open and transparent selection procedure. Carrerasleaders is addressed to boost career perspective of researchers from a three-dimensional perspective: leadership, independence, and consolidation. This is a world-wide unique postdoctoral program that covers the entire spectrum of research and innovation in blood cancers and goes from understanding disease biology to the implementation of products and processes in the market and into the clinical practice through the development of a global translational approach. Applicants will have complete freedom of research choice within the scope of blood cancers and will be offer highly attractive working conditions and a healthy, inspiring and creative working environment. CarrerasLeaders is designed based on the following objectives: 1. Training the next generation of scientist leaders to advance on the cure of blood cancers, multiplying each one’s skills sets and networks via targeted Career Development Plans and mentoring. 2. Improve the quality of blood cancers postdoctoral research training, more targeted addressed to the researchers and societal needs. 3. Enhanced cooperation and transfer knowledge between sectors and disciplines. 4. Enable outstanding junior researchers to develop their research careers to an advanced and more independent level in a leading institution such as IJC. 5. Increase the competitiveness of the IJC blood cancers community

Acute myeloid leukemia (AML) is a heterogeneous group of diseases caused by acquired cytogenetic and molecular alterations in hematopoietic progenitor cells. There is a substantial need to develop new therapeutic approaches to AML; however, the genetic heterogeneity of AML constitutes a barrier for the development of targeted therapies. Leukemia relapse after treatment is most often caused by a subgroup of cells commonly referred to as leukemia initiating cells (LICs), which are resistant to chemotherapy. It is thought that this resistance is the result of several properties unique to LICs, including their dormant and metabolically inactive state, making them less susceptible to genotoxic drugs. The localization of the LICs in the hypoxic bone marrow niche has been proposed as a driving factor for dormancy. The HIF (hypoxia-inducible factor) family of transcription factors mediates cellular adaptation to hypoxia. While the role of HIFs in the pathogenesis of solid tumors is quite well established, they have only recently been suggested as key regulators of LICs in specific types of leukemia. Yet, results to date are highly controversial, with some studies supporting an oncogenic activity for HIFs and others pointing to a tumor suppressor role. We propose a broad transcriptional study of human AML classified by cytogenetic criteria and disease stage (diagnosis vs relapse). We will focus on HIF-regulated target genes in the LIC subgroup and evaluate LIC heterogeneity using state-of-the-art single-cell technologies. Our results should extend our understanding of the ability of LICs to survive cytotoxic therapy and help to identify candidate targets for clinical application. The use of AML patient samples and single-cell techniques included in this proposal will increase my scientific knowledge and practical experience. I will also benefit from the complementary planned activities of the action, empowering me to become an independent investigator in the near future.

Background: Thalassemia is the most commonly inherited genetic disorders,. Thalassemic patients have to receive regular transfusion to sustain life, as a result of thetransfusion accumulate iron overload in the body that require a treatment with iron chelators. Iron overload and iron chelators cause alot of cardiac, hepatic and endocrine complications such as delayed puberty, hypogonadism, osteoporosis, diabetes, hypothyroidism and hypopathyroidism. Although thalassemic patients have seventy percent with disabilities, they desire a and quality of life similar to peers. Thalassemia is very serious health problem and a total 6000 thalassemic patients are followed up at Hospitals of Ministry of Health and University in Turkey. Endocrine complications were important for quality life in thalassemic patients but there are not standart protocols, quides, and regular follow-up. The aims of project were to prepare a guide including regular following up patients, to train doctors and to maintain better quality life for thalassemic patients.The responsibilities of Partners: Project Coordinator: Akdeniz Kan Hastalıkları Vakfı (AKHAV) completed Practical Guide for Effective Colloabration Preparation (PGEC), Web page, Time Table, Road Map, Financial procedures, organization of Education programs.Governorship of Antalya (CEUPA) organised the Opening anc Closing Meetings Brochures, banners, posters. In addition, Monitoring and evaluotion report was maintained by CEUPA. Antalya Training and Research Hospital (ATRH) created Patient tracking, Flow Chart for doctors. Antalya Thalassemia Association created Mobile application program for patients. Private Accredited Quisisana Hospital of Ferrara (FQH) from Italy organized the Vocational Educational Trainers Meeting in Ferrara. Barcelona University, Josep Carrera Institute (BUJCI) from Spain was responsible ICT Based Learning.Project Activities: Four Translational Project Meetings (TPM) have been done by partners in Turkey(2), Italy and Spain. Six local meetings have been done for following up to Project together with local partners in Antalya. Six E- magazines , one E-Book and Seven short videos were published at web page. Three manuscripts were published at the Journal of Endothal in Italy. A manuscript was published at the Journal of Pediatric Endocrinology Reviewer. Training of trainers: A total 20 selected trainers have been trained five days on thalasemia, endocrine complications and good practise health care and following the patient and they issued with a certificate on March 4-8, 2018 in Ferrara-Italy. Educational book: After training in Italy, all trainers have written an educational book. Flow chart and the patient follow-up guide: The trainers have prepared a flow chart and guide. Thalassemia Seminar: Ministry of Health invited one specialist each city from Turkey, thus 100 doctors and nurses 60 different cities has been participated to Thalassemia Seminar on December 10-12, 2018 in Antalya. Trainers who trained in Italy, prepared a Educational book, flow chart and the patient follow-up guide, till to thalassemia seminar. They educated all participants in two days. Mobile application: ATA has prepared a mobile application to doctors and patients for regular following patients .Impacts and long term benefits: In Turkey,there are a total 6000 patients with thalassemia and about 50% of patients with them have endocrine problems in Turkey. In Thalassemia Seminar, we invited all doctors who following up patients in Turkey. They were educated on endocrine complications of thalassemia and received a book, guide and flow chart for following patients. Thus a total of 3000 patients live with endocrine problems they will be benefited as indirectly in long term. In European and World, Project has been disseminated three papers were published in The Journal of Endo-Thal in Italy, one paper was published in the journal of Reviewer of Pediatric Endocrinology. In addition, six E- magazines an one E-Book have been implemented to web page for every body with free of charge. Thus, this Project has been disseminated to doctors in other countries such as European, Middle East and East Asia throught International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) Thus all patients in other countries will be benefited as indirectly in long term.

Haematological malignancies (HM), also known as blood cancers, are a heterogeneous and complex group of multicausal diseases that can’t be easily diagnosed nor treated. Nowadays most treatments are extremely complex, and advances in patient diagnosis and therapies slow due to the low number of patients per centre. Thus, there is a need to harmonise, store, and analyse the current HM information to speed-up and support the decision-making process for patients’ access to new therapies. HARMONY PLUS takes advantage of the capabilities of the HARMONY Big Data platform to match these unmet needs by expanding its scope to incorporate myeloproliferative neoplasms, including chronic myeloid leukemia, polycythaemia vera, essential thrombocythaemia, and myelofibrosis; and lymphoproliferative disorders, including Hodgkin’s lymphoma, Waldenström macroglobulinemia and all the other rare HMs not covered by HARMONY Project. In parallel, HARMONY PLUS will continue to refine and define the Core Outcome Sets (COS), especially for these new HMs to ensure the use by researchers of useful common outcomes relevant to all stakeholders. As previously accomplished in HARMONY, HARMONY PLUS is committed to pursue the maximum ethical and legal requirements, particularly to ensure patient’s right to privacy. Data-driven research within Europe will be enhanced by converting the current HARMONY platform into an Integrated Services Platform to serve as a valuable tool to support clinical trial design and use of available data as a control arm. This platform, combined with a HaemoDatabank repository with information about HMs patient biological samples across Europe, will facilitate a more efficient research and clinical trial design, and consequently will promote collaborations with recognised databases outside Europe. From the regulatory point of view, HARMONY PLUS will be a valuable technology tool during the evaluation of new treatments and drugs by also considering the patients’ needs.