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(Adnkronos Salute) - Uno studio internazionale guidato dall'Italia svela un nuovo meccanismo molecolare all'origine di una forma di leucemia molto diffusa nei bambini. A coordinare la ricerca è l'Italia con l'università Sapienza di Roma. Il lavoro, pubblicato su 'Oncogene', apre a nuove tecniche di monitoraggio e a nuove terapie. La leucemia linfoblastica acuta (Lla) - spiegano dalla Sapienza - è un tumore ematologico aggressivo a rapida evoluzione che colpisce i linfociti T, arrestandoli in una fase immatura. Tra le leucemie acute infantili, circa il 60% è rappresentato proprio dalla Lla. Anomalie genetiche bloccano la differenziazione dei precursori delle cellule T nel timo, una ghiandola situata nel mediastino, davanti al cuore, e favoriscono una proliferazione cellulare anomala. Le cellule leucemiche in accumulo infiltrano poi il midollo osseo, provocando la malattia. Nel 60% dei pazienti con Lla-T si riscontrano mutazioni che portano a un'iperattività del sistema di segnalazione Notch. La chemioterapia intensiva può curare molti dei malati, ma un'alta percentuale di pazienti pediatrici e soprattutto adulti è soggetta a ricadute con prognosi sfavorevole. I recettori Notch possono infatti contribuire alla resistenza alla chemio, rendendo necessaria la ricerca di nuovi approcci per contrastare il suo apporto alla progressione della Lla-T.Il nuovo studio, condotto dal Dipartimento di Medicina sperimentale della Sapienza in collaborazione con il Dipartimento di Medicina molecolare, e frutto di una rete di collaborazioni con altri enti di ricerca - hanno partecipato in particolare la Weill Cornell Medicine di New York per gli Usa, e nel nostro Paese anche l'Istituto italiano di tecnologia (Iit) di Roma, l'Azienda ospedaliera dei Colli Monaldi di Napoli, l'università di Roma Tor Vergata, l'Istituto nazionale tumori Regina Elena capitolino, l'università di Padova e quella di Perugia - indica come la proteina Notch moduli i meccanismi epigenetici di regolazione del recettore CXCR4 attraverso l'interazione con particolari microRna. Così contribuisce al blocco dello sviluppo e della differenziazione delle cellule T, e sovverte completamente le funzioni del timo, inducendone una precoce involuzione.Il risultato - illustra una nota - è stato ottenuto attraverso un modello transgenico per il gene Notch3, che ha permesso di verificare molte delle caratteristiche molecolari e cellulari della Lla-T, e grazie all'impiego di molteplici tecniche avanzate di citofluorimetria e di analisi molecolare. I dati epigenetici sono stati confermati mediante l'utilizzo di modelli di xenotrapianto ottenuti utilizzando campioni di pazienti affetti da Lla-T, trapiantati in modelli sperimentali murini. "Il lavoro conta, non solo fra i primi nomi, nostri giovani ricercatori in Italia ed all'stero - rimarca Maria Pia Felli, autrice dell'articolo - che con professionalità hanno condotto esperimenti complessi e fondamentali per questo studio, dimostrando passione ed entusiasmo per la ricerca scientifica. La specifica competenza fornita da ogni singolo autore e dai vari centri di ricerca coinvolti ha permesso la realizzazione di questo progetto". I risultati ottenuti fanno progredire la conoscenza scientifica sulla Lla e suggeriscono questi microRna come nuovi addizionali biomarker molecolari per il monitoraggio e, nel futuro, per avanzate strategie terapeutiche contro la neoplasia. di Adnkronos   19-07-2024 - 18:00 Link copiato Commenti Leggi la Netiquette

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