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HEMatopoietic cell IDentity : genetic and epigenetic regulation in normal and malignant hematopoiesis

Final Report Summary - HEM_ID (HEMatopoietic cell IDentity : genetic and epigenetic regulation in normal and malignant hematopoiesis)

In hematopoiesis, failure to maintain homeostasis and regenerative functions result in a multitude of hematological malignancies, including myelodysplastic syndromes, lymphomas and leukemias, that represent a medical challenge and a large socioeconomic burden because of the large number of affected patients of all age groups.
The focus of Hem-ID was a highly integrated approach to study the functional interactions between the genetic regulatory circuits orchestrated by transcription factors –TFs-, (that direct the progressive cell type specification) and epigenetic mechanisms (that establish the “cellular memory” that fixes cell fate decisions during differentiation) in physiological hematopoiesis and in leukemia with the final goal of formulating novel diagnostic/prognostic markers and therapeutic approaches in treating leukemias.

To reach this goal HEM_ID brought together 13 laboratories from 7 different European countries and enrolled 12 Fellows of 8 different nationalities
The strength of Hem-ID ITN resided in the high quality multidisciplinary -but strictly integrated- expertise and technological platforms covering the complete pathway from basic research to its clinical exploitation- contributed from both public Institutions and Private sector and made available to Hem-ID Fellows.
Besides research, an integrated training program of scientific and complementary activities has been offered to HEM-ID Fellows to complement and strengthen their career development.
Thanks to a strict collaboration and to the implementation of a shared platform of technologies, HEM_ID led to major advances in the knowledge of the molecular mechanisms governing normal and malignant hematopoiesis, with the identification and validation of novel protein-protein interactions in normal and malignant hematopoietic cells. These networks constitute candidate targets for the development of new diagnostic markers and therapeutic approaches to treat hematological diseases. In particular, we identified molecular networks involving different Transcription Factors (Sox6 in erythropoiesis for UNIMIB; Ikaros family members in Hematopoietic Stem cells, in T cells and in B-ALL, GIE-CERBM, ICURIE; Mll-interactome, CeMM). The molecular dynamics of TFs binding to chromatin (CNRS) and the modulation of chromatin structure associated to the integration of histone variants (UJF) were characterized in vitro and in vivo. FT provided a precious scientific support in evaluating the relevance of the identified genes/pathways for the understanding of the molecular basis of leukemias. Finally, the two companies participating to our Network developed an optimized protocol for high throughput transfection and phenotypic screening in human erythroleukemic cells (NMS) and implemented a series of bioinformatical analyses (SBS) required to analyze the large dataset generated within HEM_ID.
HEM_ID success is demonstrated by several scientific articles published by the members of HEM_ID with the participation of Fellows, who were all enrolled in PhD Programs at the participating Institution, including the two students working in NMS and SBS and that will all be awarded a PhD title within the end of 2016. Our website received 47248 Visits from December 2011 and contributed to disseminate HEMID research and to promote MSCA actions to a very wide audience. Our Fellows had the opportunity to develop a solid basis for their future career and to build up a solid scientific network of relationships in the field of the European research in hematology. Their scientific and personal experience within HEM_ID is recounted by themselves in the booklet that they assembled at the end of the HEM_ID program, available on the Hemid website (