Academic Journal
Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL.
| العنوان: | Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. |
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| المؤلفون: | Tzoneva G, Perez Garcia A, Carpenter Z, Khiabanian H, Tosello V, Allegretta M, Paietta E, Racevskis J, Rowe JM, Tallman MS, Hof J, Kirschner Schwabe R, Palomero T, Rabadan R, Ferrando A., PAGANIN, MADDALENA, BASSO, GIUSEPPE |
| المساهمون: | Tzoneva, G, Perez Garcia, A, Carpenter, Z, Khiabanian, H, Tosello, V, Allegretta, M, Paietta, E, Racevskis, J, Rowe, Jm, Tallman, M, Paganin, Maddalena, Basso, Giuseppe, Hof, J, Kirschner Schwabe, R, Palomero, T, Rabadan, R, Ferrando, A. |
| بيانات النشر: | Elsevier BV:PO Box 211, 1000 AE Amsterdam Netherlands:011 31 20 4853757, 011 31 20 4853642, 011 31 20 4853641, EMAIL: nlinfo-f@elsevier.nl, INTERNET: http://www.elsevier.nl, Fax: 011 31 20 4853598. |
| سنة النشر: | 2013 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| مصطلحات موضوعية: | leukemia |
| الوصف: | Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Despite intensive chemotherapy, 20% of pediatric patients and over 50% of adult patients with ALL do not achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most substantial challenge in the treatment of this disease. Using whole-exome sequencing, we identify mutations in the cytosolic 5′-nucleotidase II gene (NT5C2), which encodes a 5′-nucleotidase enzyme that is responsible for the inactivation of nucleoside-analog chemotherapy drugs, in 20/103 (19%) relapse T cell ALLs and 1/35 (3%) relapse B-precursor ALLs. NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts. These results support a prominent role for activating mutations in NT5C2 and increased nucleoside-analog metabolism in disease progression and chemotherapy resistance in ALL. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/23377281; info:eu-repo/semantics/altIdentifier/wos/WOS:000316040700032; volume:19; issue:3; firstpage:368; lastpage:371; numberofpages:4; journal:NATURE MEDICINE; http://hdl.handle.net/11577/2553289; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84875158235 |
| DOI: | 10.1038/nm.3078 |
| الاتاحة: | http://hdl.handle.net/11577/2553289 https://doi.org/10.1038/nm.3078 |
| رقم الانضمام: | edsbas.9D7DE5E4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/nm.3078 |
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