Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia
| Autor: | Wolf-Karsten Hofmann, Claudia D. Baldus, Julia Thibaut, Cornelia Schlee, Andrea Stroux, Dieter Hoelzer, Max Mossner, Stefan Schwartz, Clara D. Bloomfield, Eckhard Thiel, Nicola Goekbuget, Thomas Burmeister |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty F-Box-WD Repeat-Containing Protein 7 Adolescent T-Lymphocytes Ubiquitin-Protein Ligases Editorials and Perspectives Cell Cycle Proteins Biology medicine.disease_cause Cohort Studies Young Adult Immunophenotyping Internal medicine Acute lymphocytic leukemia hemic and lymphatic diseases medicine Humans Cell Lineage Receptor Notch1 Survival rate BAALC Aged Mutation Hematology F-Box Proteins Cancer hemic and immune systems Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Prognosis Survival Rate Leukemia embryonic structures cardiovascular system Cancer research Original Article Female sense organs biological phenomena cell phenomena and immunity |
| Zdroj: | Haematologica. 94(10) |
| ISSN: | 1592-8721 |
| 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: | OpenAIRE |
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