Mazzarini, Maria
(2024)
Contribution of cytokines to the etiology and progression of Primary Myelofibrosis, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Scienze biomediche e neuromotorie, 36 Ciclo. DOI 10.48676/unibo/amsdottorato/11253.
Documenti full-text disponibili:
|
Documento PDF (English)
- Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (722kB)
|
Abstract
Primary Myelofibrosis (PMF) is the end-stage of Philadelphia-negative myeloproliferative neoplasms (MPN) and is characterized by fibrosis and hematopoietic failure in bone marrow, with a consequential migration of the malignant hematopoietic stem cells (HSC) in the spleen where they induce ineffective haematopoiesis. To date, available therapies for PMF are still palliative and do not halt the progression of this neoplasm.
During my PhD years, our laboratory investigated the factors promoting the onset and progression of PMF. In our PMF mice model, Gata1low mouse, we studied the role of the interaction of HSC niche with megakaryocytes and HSC localization in the bone marrow during their division and cycle. We observed the inflammation and the main protagonists (LNC-2, CXCL1, and TGF-β) of this process and how their level changes before and after the onset of the disease. We investigated the different megakaryocyte populations in the fibrotic environment in different organs (lung and bone marrow) to define the megakaryocytes implicated in this process. In human samples, we described different ultrastructural abnormalities of megakaryocytes from the bone marrow and the spleen, identifying a possible different metabolism in those two populations.
In conclusion, we highlighted the intricated crosstalk between the megakaryocytes, the niche and HSC in PMF. We identified megakaryocytes-dependent cytokines altering the homeostasis of the niche and HSC. Those cytokines could be used as alternative therapeutic targets. Furthermore, we observed different megakaryocytic populations in different organs, providing new prospective on the role of megakaryocytes in different microenvironments.
Abstract
Primary Myelofibrosis (PMF) is the end-stage of Philadelphia-negative myeloproliferative neoplasms (MPN) and is characterized by fibrosis and hematopoietic failure in bone marrow, with a consequential migration of the malignant hematopoietic stem cells (HSC) in the spleen where they induce ineffective haematopoiesis. To date, available therapies for PMF are still palliative and do not halt the progression of this neoplasm.
During my PhD years, our laboratory investigated the factors promoting the onset and progression of PMF. In our PMF mice model, Gata1low mouse, we studied the role of the interaction of HSC niche with megakaryocytes and HSC localization in the bone marrow during their division and cycle. We observed the inflammation and the main protagonists (LNC-2, CXCL1, and TGF-β) of this process and how their level changes before and after the onset of the disease. We investigated the different megakaryocyte populations in the fibrotic environment in different organs (lung and bone marrow) to define the megakaryocytes implicated in this process. In human samples, we described different ultrastructural abnormalities of megakaryocytes from the bone marrow and the spleen, identifying a possible different metabolism in those two populations.
In conclusion, we highlighted the intricated crosstalk between the megakaryocytes, the niche and HSC in PMF. We identified megakaryocytes-dependent cytokines altering the homeostasis of the niche and HSC. Those cytokines could be used as alternative therapeutic targets. Furthermore, we observed different megakaryocytic populations in different organs, providing new prospective on the role of megakaryocytes in different microenvironments.
Tipologia del documento
Tesi di dottorato
Autore
Mazzarini, Maria
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Primary Myelofibrosis, fibrotic environment, HSC niche, megakaryocytes, pro-inflamatory cytokines
URN:NBN
DOI
10.48676/unibo/amsdottorato/11253
Data di discussione
21 Marzo 2024
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Mazzarini, Maria
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Primary Myelofibrosis, fibrotic environment, HSC niche, megakaryocytes, pro-inflamatory cytokines
URN:NBN
DOI
10.48676/unibo/amsdottorato/11253
Data di discussione
21 Marzo 2024
URI
Statistica sui download
Gestione del documento: