Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia
| Autor: | Claudia D. Baldus, Julia Thibaut, Nicola Goekbuget, Andrea Stroux, Cornelia Schlee, Max Mossner, Thomas Burmeister, Stefan Schwartz, Clara D. Bloomfield, Dieter Hoelzer, Eckhard Thiel, Wolf-Karsten Hofmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Haematologica, Vol 94, Iss 10 (2009) |
| Druh dokumentu: | article |
| ISSN: | 0390-6078 1592-8721 |
| DOI: | 10.3324/haematol.2008.005272 |
| Popis: | Background NOTCH1 mutations have been associated with a favorable outcome in pediatric acute T-lymphoblastic leukemia. However, the results of studies on the prognostic significance of NOTCH1 mutations in adult T-lymphoblastic leukemia remain controversial.Design and Methods Here we have investigated the prognostic impact of mutations in the NOTCH1 pathway, in particular, the NOTCH1 and FBXW7 genes, in a large cohort of adult patients with T-lymphoblastic leukemia (n=126). We determined the occurrence of mutations in NOTCH1 and FBXW7 by DNA amplification and direct sequencing of polymerase chain reaction products.Results Mutations were identified in 57% and 12% of the NOTCH1 and FBXW7 genes, respectively. The characteristics of patients carrying NOTCH1 and/or FBXW7 (NOTCH1-FBXW7) mutations were similar to those with wild-type genes. Patients with NOTCH1-FBXW7 mutations more often showed a thymic immunophenotype (p=0.001). In the overall cohort, no significant differences were seen in the complete remission or event-free survival rates between patients with mutated or wild-type NOTCH1-FBXW7 (p=0.39).Conclusions NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of adult patients with T-lymphoblastic leukemia, but there was a trend towards a favorable prognostic impact of NOTCH1-FBXW7 mutations in the small subgroup of patients with low-risk ERG/BAALC expression status. Our findings further confirm the high frequency of NOTCH1 mutations in adult T-lymphoblastic leukemia. |
| Databáze: | Directory of Open Access Journals |
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