The Myeloid Neoplasms Biology and Outcome Project

During recent years, considerable progress has been made in deciphering the molecular genetic and epigenetic basis of myeloid neoplasms and in defining new diagnostic and prognostic as well as predictive markers. Myeloid neoplasms are categorized according to the current WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues based on the revision of 2016 [1]. This includes Myeloproliferative neoplasms (MPN), Mastocytosis, Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2, Myelodysplastic/myeloproliferative neoplasms (MDS/MPN), Myelodysplastic syndromes (MDS), Myeloid neoplasms with germ line predisposition, Acute myeloid leukemia (AML) and related neoplasms (i.e. Myeloid sarcoma and Myeloid proliferations related to Down syndrome), Blastic plasmacytoid dendritic cell neoplasm and Acute leukemia of ambiguous lineage (Table 1).

A growing number of recurring genetic changes are recognized in the current WHO 2016 classification of myeloid neoplasms [2] and additional molecularly defined subgroups as well as new entities are expected to be included in future versions. Furthermore, novel therapies are now available and being developed, which target specific genetic lesions, and several surface antigens are being explored as targets for immunotherapy-based treatment strategies, e.g. CAR-T-cell therapy [3].

Although the WHO 2016 classification represents an enormous progress in terms of reliability, validity and objectivity, there are still huge diagnostic uncertainties left [4-18] and the field of targeted therapy [19-25] in myeloid neoplasms is just at its beginning. Furthermore, clonal evolution and transition from one entity to another is a clinically relevant issue [26-30].

Thus, key areas of interest are:

• Systematic collection and evaluation of comprehensive clinical information from patients with myeloid neoplasm, including morphomolecular disease subtype, as well as drug treatments, radiation therapy, surgical procedures and long-term follow-up data
• Systematic collection and evaluation of comprehensive biological specimens and information from patients with myeloid neoplasms, including data on the genomic, transcriptomic, epigenomic and proteomic "landscapes" as well as expression of surface antigens of myeloid disease subtypes, to identify novel prognostic and predictive parameters as well as entry points for targeted therapeutic interventions
• Regular assessment of patient reported outcomes

The above challenges are ideally met by a registry study with a sufficient population size in order to answer relevant questions in rare cancer entities. The aim is to set up a registry study that covers systematic and comprehensive clinical data acquisition. In addition, the banking of tumor and germline samples from patients with myeloid neoplasms is intended by all patients. This resource will spur patient-oriented investigations into relationships between clinical and biological parameters in myeloid neoplasms and lay the groundwork for novel, molecular mechanism- and immunotherapy-based treatment approaches in poorly understood and difficult-to-treat subsets.