NOTCH1/FBXW7mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study
In: Blood, Jg. 113 (2009-04-23), Heft 17, S. 3918-3924
serialPeriodical
Zugriff:
Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1and/or FBXW7mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and 34 cases (24%) had FBXW7mutations (21 cases had both NOTCH1and FBXW7mutations); 40 cases (28%) were wild type for both. There was no significant correlation between NOTCH1and/or FBXW7mutations and clinico-biologic features. Median event-free survival (EFS) and overall survival (OS) were 36 versus 17 months (P= .01) and not reached versus 32 months (P= .004) in patients with NOTCH1and/or FBXW7mutations versus other patients, respectively. Multivariate analysis showed that the presence of NOTCH1/FBXW7mutations was an independent good prognostic factor for EFS and OS (P= .02 and P= .01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1or FBXW7mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL.
Titel: |
NOTCH1/FBXW7mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study
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Autor/in / Beteiligte Person: | Asnafi, Vahid ; Buzyn, Agnès ; Le Noir, Sandrine ; Baleydier, Frédéric ; Simon, Arnauld ; Beldjord, Kheira ; Reman, Oumedaly ; Witz, Francis ; Fagot, Thierry ; Tavernier, Emmanuelle ; Turlure, Pascal ; Leguay, Thibaut ; Huguet, Françoise ; Vernant, Jean-Paul ; Daniel, Francis ; Béné, Marie-Christine ; Ifrah, Norbert ; Thomas, Xavier ; Dombret, Hervé ; Macintyre, Elizabeth |
Zeitschrift: | Blood, Jg. 113 (2009-04-23), Heft 17, S. 3918-3924 |
Veröffentlichung: | 2009 |
Medientyp: | serialPeriodical |
ISSN: | 0006-4971 (print) ; 1528-0020 (print) |
DOI: | 10.1182/blood-2008-10-184069 |
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