A new strategy for early detection of the risk of transformation into acute leukaemia in patients with myelofibrosis
An important new scientific discovery has been made by the research group led by Prof. Rossella Manfredini, head of the Genomics and Transcriptomics programme at Unimore's “Stefano Ferrari” Centre for Regenerative Medicine.
The study deals with molecular alterations that affect the haemopoietic stem cell and cause chronic blood neoplasms such as myelofibrosis to rapidly fatal acute leukaemias.
Myelofibrosis is a blood cancer for which there is no definitive cure. Through the use of new single-cell technologies, which analyse the genome, transcriptome and chromatin accessibility as a whole, it is now possible to study the mechanisms of leukaemic transformation in detail, thus identifying new potential therapeutic targets.
The research, one of the first worldwide on this topic, was supported by the AIRC Foundation for Cancer Research, in collaboration with the team of Prof. Alessandro Vannucchi of the University of Florence and Prof. Matteo Della Porta of Humanitas University. The study analysed at the single-cell level in myelofibrosis stem cells the alterations that lead to the transformation of this chronic disease into acute leukaemia, the most frequent cause of death from this disease, as it does not respond to conventional therapeutic treatments.
“Through this study”' says Prof. Rossella Manfredini of Unimore, “it was possible to observe how the stem cell clones that drive leukaemic transformation are characterised by mutations and variations in the copy number of certain genes that are fundamental for proper haemopoiesis. Therefore, we were able to identify, in a relatively large number of patients, in the chronic phase of the disease, leukaemic cell clones that are present even in a very small percentage and then expand during disease progression
“Reconstructing the clonal architecture of the tumour stem population, determined by the progressive acquisition of pathogenic mutations in the DNA, and how this population diversifies and evolves over time, allows us to understand the molecular mechanisms underlying the onset and leukaemic transformation of myeloproliferative neoplasms,” says Dr Chiara Carretta, coauthor of the article.
“This study,” concluded Prof. Manfredini, 'just published in the prestigious American Journal of Haematology of the Wiley Group, makes it possible to classify these patients at high risk of transformation and to predict a more accurate prognosis with the possibility of identifying new targets for the development of patient-specific therapies with a view to personalised medicine”.
Rossella Manfredini
She graduated in Biological Sciences from the University of Modena in 1988 with a mark of 110/110 with honours. In 1994, she obtained a PhD in Experimental Haematology and in 1996 her specialisation in Biochemistry and Clinical Chemistry. A recipient of AIRC and Lega Italiana Lotta contro i Tumori grants, she was a postdoctoral fellow at Temple University in Philadelphia (US), obtaining a US patent in 1998 for “Use of AS c-fes and ATRA oligonucleotides in M3-type leukaemias”. She has been Full Professor of Applied Biology at UNIMORE since 2013. She is author of 113 scientific publications in high-impact international journals. She has been working for more than 30 years on the biology of stem cells, both normal and pathological, with particular reference to the molecular mechanisms underlying the processes of self-renewal, proliferation and differentiation. Her main research topics are: molecular and functional characterisation of normal and leukaemic haemopoietic stem cells, study of clonal heterogeneity of the stem compartment in chronic myeloproliferative diseases, identification of new therapeutic targets in myeloid neoplasms.
Unimore's “Stefano Ferrari” Centre for Regenerative Medicine is a centre of excellence on the international research scene in the characterisation of epithelial stem cells and their clinical application in cell and gene therapy, thanks also to its state-of-the-art instrumentation and its painstaking work to comply with European regulations on GMP (Good Manufacturing Practice) certification. CMR ( https://www.cmr.unimore.it/ ) also hosts the Interdepartmental Centre for Stem Cells and Regenerative Medicine .
In the photo from the left: Sebastiano Rontauroli, Sandra Parenti, Chiara Carretta, Rossella Manfredini, and Matteo Bertesi
Categorie: International - english
Articolo pubblicato da: Ufficio Stampa Unimore - ufficiostampa@unimore.it il 06/07/2023