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The European Hematology Association (EHA) previously published the EHA Research Roadmap in 2016, highlighting achievements in diagnostics and treatment of blood disorders, as well as informing European policymakers of the urgent clinical and scientific needs and research priorities in the field of hematology. There have been numerous developments and advances in hematology since 2016, which justifies an updated Research Roadmap. Döhner and colleagues, including the chair of the MDS Hub Theo de Witte, co-chair of the AML Hub Charles Craddock, MPN, AML, and MDS Hub steering committee members Alessandro Vannucchi, Claire Harrison, Gert Ossenkoppele, Jorge Sierra, Pierre Fenaux, and Eva Hellstrom-Lindberg, and AML Hub scientific advisory board members Lars Bullinger, Agnieszka Wierzbowska, and Hervé Dombret, have recently published a section on malignant myeloid diseases in the updated EHA Research Roadmap, which outlines the most urgent priorities in this area.1 The Research Roadmap includes myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), and covers research contributions from Europe, proposed direction for future research and its potential impact for each. We are pleased to provide a summary here.
MDS are clonal disorders of hematopoietic stem cells (HSCs), characterized by their propensity to evolve into AML. The incidence rate of MDS is 4 per 100,000 people per year, but increases greatly over the age of 60 years, with >30,000 new cases expected each year in Europe. Recent studies have provided evidence of healthy individuals acquiring somatic mutations of the most frequently mutated genes in MDS with ageing, a state defined as clonal hematopoiesis of indeterminate potential (CHIP), increasing the risk of hematologic malignancies, cardiovascular disease, and all-cause mortality. Current treatment options for MDS range from allogeneic HSC transplantation (HSCT), azacitidine, erythropoiesis-stimulating agents, lenalidomide, red cell transfusion, and luspatercept.
Several pivotal studies have been performed in Europe, including major advances in understanding the genetic mechanisms of MDS. European researchers have also contributed to developing effective treatments including erythropoietin, azacitidine, lenalidomide, and luspatercept, as well as elucidating the genetic predisposition to MDS and other myeloid neoplasms in pediatric hematology.
The proposed research has the potential to decipher the cellular and molecular mechanisms of MDS, enhancing the identification of effective targeted interventions. Identifying the precursors to MDS and MDS/MPN will also help develop effective strategies focused on early diagnosis and interventions aimed at preventing clonal expansion and progression.
There are nearly 17,000 newly diagnosed patients with AML each year in Europe, making AML the most common form of acute leukemia in adults. The incidence of AML increases with age, implying a further increase in future years. Although an understanding of the molecular complexity of AML has led to the refinement of risk stratification and personalized therapeutic strategies, the prognosis and cure rates in both young and older patients remain poor. Lately, allogeneic HSCT has become a potentially curative treatment strategy for AML, owing to donor availability coupled with reduced intensity conditioning regimens.
Collaboration between European trial groups has become important for the accelerated delivery of new drugs and transplant therapies. One such alliance is the combined effort of European trial groups leading to the approval of gemtuzumab ozogamicin, an antibody-drug conjugate targeting CD33. The diagnosis and management of AML has transformed internationally, based on the European Leukemia Network (ELN) recommendations, including minimal residual disease (MRD) assessment, which play an important role in harmonization and standardization of MRD monitoring techniques. European researchers have also elucidated the biology of AML with mutated, translocated, or overexpressed genes, and germline mutations predisposing to AML.
Future research will help to decipher the molecular heterogeneity of AML and identify gene-to-gene interactions, instrumental in refining MRD assessment and developing personalized treatment strategies. Transplant outcomes will improve with accelerated delivery of prospective transplant trials. Particular attention should be paid to the management of older patients with AML, owing to their distinct biology and poor outcomes.
MPN are chronic, incurable disorders of HSCs, including polycythemia vera, essential thrombocythemia, prefibrotic and overt primary myelofibrosis, and post-polycythemia vera/post-essential thrombocythemia myelofibrosis, usually occurring in middle-advanced age patients, but recently diagnosed more frequently in younger people. Patients with MPN suffer from major thrombotic events and hemorrhages and have an impaired quality of life.
The World Health Organization (WHO) diagnostic criteria was revolutionized by the breakthrough discoveries of JAK2V617F, JAK2 exon 12, and CALR mutations by European hemopathologists and the identification of genetic haplotypes predisposing to MPN. European researchers, in collaboration with American colleagues, developed various new disease classification criteria and risk scores such as the Mutation-Enhanced International Prognostic Scoring System for Transplant Age Patients (MIPSS-70) for primary myelofibrosis. The International Prognostic Scoring System (IPSS) and the Dynamic International Prognostic Scoring System (DIPSS) were also developed in Europe, along with some crucial studies leading to approval of the JAK1 and JAK2 inhibitors ruxolitinib and fedratinib.
Further research from population-derived studies is likely to advance the development of personalized medicine approaches, ranging from diagnostic categories to alternative therapies based on individual risk ratio.
The EHA Research Roadmap for malignant myeloid diseases outlines the main research and policy priorities. Overall, a better understanding of CHIP and the genetic and epigenetic complexity of myeloid diseases, development of new therapeutic targets, and refinement of MRD techniques are the direction of future research, anticipated to further improve the outcomes in patients with MDS, AML, and MPN.
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