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EnglishChronic lymphocytic leukemia (CLL) clones are characterized by loss of a critical region in 13q14.3, (del(13)(q14)) involving the microRNA (miRNA) cluster miR-15a and miR-16-1. We have investigated the effects of replacement of miR-15a and miR-16-1. CLL cells transfected with these miRNA mimics exhibited a decrease in cell viability in vitro and impaired capacity for engraftment and growth in NOD/Shi-scid,3cnull (NSG) mice. No synergistic effects were observed when the two miRNA mimics were combined. The phenomena were not restricted to CLL with the del(13)(q14) lesion. Similar effects induced by miRNA mimics were seen in cells with additional chromosomal abnormalities with the exception of certain CLL clones harboring TP53 alterations. Administration of miRNA mimics to NSG mice previously engrafted with CLL clones resulted in substantial tumor regression. CLL cell transfection with miR-15a and miR-16-1-specific inhibitors resulted in increased cell viability in vitro and in an enhanced capacity of the engrafted cells to grow in NSG mice generating larger splenic nodules. These data demonstrate that the strong control by miR-15a and miR-16-1 on CLL clonal expansion is exerted also at the level of full-blown leukemia and provide indications for a miRNA-based therapeutic strategy.
| Data di pubblicazione: | 2017 | |
| Titolo: | Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia: Implication for therapy | |
| Autori: | Cutrona, G.; Matis, S.; Colombo, M.; Massucco, C.; Baio, G.; Valdora, F.; Emionite, L.; Fabris, S.; Recchia, A. G.; Gentile, M.; Neumaier, C. E.; Reverberi, D.; Massara, R.; Boccardo, S.; Basso, L.; Salvi, S.; Rosa, F.; Cilli, M.; Zupo, S.; Truini, M.; Tassone, P.; Calabrese, M.; Negrini, Massimo; Neri, A.; Morabito, F.; Fais, F.; Ferrarini, M. | |
| Rivista: | LEUKEMIA | |
| Keywords: | Animals; Cell Line; Cell Proliferation; Cell Survival; Chromosome Deletion; Chromosomes, Human, Pair 13; Heterografts; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Mice; MicroRNAs; Transfection; Tumor Burden; Hematology; Cancer Research | |
| Abstract in inglese: | Chronic lymphocytic leukemia (CLL) clones are characterized by loss of a critical region in 13q14.3, (del(13)(q14)) involving the microRNA (miRNA) cluster miR-15a and miR-16-1. We have investigated the effects of replacement of miR-15a and miR-16-1. CLL cells transfected with these miRNA mimics exhibited a decrease in cell viability in vitro and impaired capacity for engraftment and growth in NOD/Shi-scid,3cnull (NSG) mice. No synergistic effects were observed when the two miRNA mimics were combined. The phenomena were not restricted to CLL with the del(13)(q14) lesion. Similar effects induced by miRNA mimics were seen in cells with additional chromosomal abnormalities with the exception of certain CLL clones harboring TP53 alterations. Administration of miRNA mimics to NSG mice previously engrafted with CLL clones resulted in substantial tumor regression. CLL cell transfection with miR-15a and miR-16-1-specific inhibitors resulted in increased cell viability in vitro and in an enhanced capacity of the engrafted cells to grow in NSG mice generating larger splenic nodules. These data demonstrate that the strong control by miR-15a and miR-16-1 on CLL clonal expansion is exerted also at the level of full-blown leukemia and provide indications for a miRNA-based therapeutic strategy. | |
| Digital Object Identifier (DOI): | 10.1038/leu.2016.394 | |
| Handle: | http://hdl.handle.net/11392/2376380 | |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
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| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2017Leukemia_Negrini.pdf | versione editoriale | Full text (versione editoriale) | NON PUBBLICO - Accesso privato/ristretto | Administrator Richiedi una copia |
| 131024215.pdf | versione preprint | Pre-print | PUBBLICO - Pubblico con Copyright | Open Access Visualizza/Apri |
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