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Year:
2009
| Volume: 17
| Issue: 3-4
| Pages: 72-77
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Review Article |
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Notch : FROM FLY WINGS TO HUMAN HEMATOLOGICAL TUMORS
Leonardo Mirandola, Sara Larocca, Katia Rea, Giovanni Palma, Paola Comi, Raffaella Chiaramonte |
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DOI:
10.2298/AOO0904072M |
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Abstract: |
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Notch history begins in 1919 with Thomas Hunt Morgan studies on fruit fly mutants. From then, this gene aroused lively interest in the scientific community since it is involved in a wide variety of processes, including morphogenesis, tissue homeostasis, and stem cell maintenance. Deregulation of Notch signaling characterizes several human tumors. Hematopoietic system is affected by mutations of Notch receptors, Notch ligands, and proteins controlling their stability. Approximately 60% T acute lymphoblastic leukemia (T-ALL) patients carry activating Notch1 mutations prompting blasts growth. In addition, multiple myeloma is characterized by Notch signaling hyper-activation due to an abnormal expression of the Jagged2 ligand; this affects not only myeloma cells, but also their interaction with bone marrow microenvironment, influencing tumor burden and bone disease. These findings make Notch a rational target of a therapeutic approach. Inhibitors of the Notch activating enzyme, a-Secretase inhibitors by acting downstream Notch receptor. Therefore, the interaction of Notch with other cancer-associated proteins should be clarified to predict the biological outcome of a Notch targeted therapy and possibly, to exploit combined treatments against the key deregulated elements in Notch-associated cancers. |
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Key words:
Receptors, Notch; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proto-Oncogene Proteins c-myc; Intracellular Signaling Peptides and Proteins; Enzyme Inhibitors;... |
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