Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL.
Although TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in...
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| Materiálatiipa: | Journal article |
| Giella: | English |
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American Society of Hematology
2015
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| _version_ | 1826282759770865664 |
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| author | Guièze, R Robbe, P Clifford, R de Guibert, S Pereira, B Timbs, A Dilhuydy, M Cabes, M Ysebaert, L Burns, A Nguyen-Khac, F Davi, F Véronèse, L Combes, P Le Garff-Tavernier, M Leblond, V Merle-Béral, H Alsolami, R Hamblin, A Mason, J Pettitt, A Hillmen, P Taylor, J Knight, S Tournilhac, O Schuh, A |
| author_facet | Guièze, R Robbe, P Clifford, R de Guibert, S Pereira, B Timbs, A Dilhuydy, M Cabes, M Ysebaert, L Burns, A Nguyen-Khac, F Davi, F Véronèse, L Combes, P Le Garff-Tavernier, M Leblond, V Merle-Béral, H Alsolami, R Hamblin, A Mason, J Pettitt, A Hillmen, P Taylor, J Knight, S Tournilhac, O Schuh, A |
| author_sort | Guièze, R |
| collection | OXFORD |
| description | Although TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in prospective trials was screened using targeted next-generation sequencing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes. We performed clustering according to both number and combinations of recurrent gene mutations. The number of genes affected by mutation was ≥2, 1, and 0 in 43 (38%), 49 (43%), and 22 (19%) respectively. Recurrent combinations of ≥2 mutations of TP53, SF3B1, and ATM were found in 22 (19%) patients. This multiple-hit profile was associated with a median progression-free survival of 12 months compared with 22.5 months in the remaining patients (P = .003). Concurrent gene mutations are frequent in patients with relapsed/refractory CLL and are associated with worse outcome. |
| first_indexed | 2024-03-07T00:48:42Z |
| format | Journal article |
| id | oxford-uuid:859b751b-5c11-42c1-af03-cc6ac262e2a1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:48:42Z |
| publishDate | 2015 |
| publisher | American Society of Hematology |
| record_format | dspace |
| spelling | oxford-uuid:859b751b-5c11-42c1-af03-cc6ac262e2a12022-03-26T21:58:43ZPresence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:859b751b-5c11-42c1-af03-cc6ac262e2a1EnglishSymplectic Elements at OxfordAmerican Society of Hematology2015Guièze, RRobbe, PClifford, Rde Guibert, SPereira, BTimbs, ADilhuydy, MCabes, MYsebaert, LBurns, ANguyen-Khac, FDavi, FVéronèse, LCombes, PLe Garff-Tavernier, MLeblond, VMerle-Béral, HAlsolami, RHamblin, AMason, JPettitt, AHillmen, PTaylor, JKnight, STournilhac, OSchuh, AAlthough TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in prospective trials was screened using targeted next-generation sequencing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes. We performed clustering according to both number and combinations of recurrent gene mutations. The number of genes affected by mutation was ≥2, 1, and 0 in 43 (38%), 49 (43%), and 22 (19%) respectively. Recurrent combinations of ≥2 mutations of TP53, SF3B1, and ATM were found in 22 (19%) patients. This multiple-hit profile was associated with a median progression-free survival of 12 months compared with 22.5 months in the remaining patients (P = .003). Concurrent gene mutations are frequent in patients with relapsed/refractory CLL and are associated with worse outcome. |
| spellingShingle | Guièze, R Robbe, P Clifford, R de Guibert, S Pereira, B Timbs, A Dilhuydy, M Cabes, M Ysebaert, L Burns, A Nguyen-Khac, F Davi, F Véronèse, L Combes, P Le Garff-Tavernier, M Leblond, V Merle-Béral, H Alsolami, R Hamblin, A Mason, J Pettitt, A Hillmen, P Taylor, J Knight, S Tournilhac, O Schuh, A Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. |
| title | Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. |
| title_full | Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. |
| title_fullStr | Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. |
| title_full_unstemmed | Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. |
| title_short | Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. |
| title_sort | presence of multiple recurrent mutations confers poor trial outcome of relapsed refractory cll |
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