Haematologica, Vol 94, Issue 10, 1383-1390 doi:10.3324/haematol.2008.005272
Copyright © 2009 by Ferrata Storti Foundation
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Acute Lymphoblastic Leukemia

Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia

Claudia D. Baldus1, Julia Thibaut1, Nicola Goekbuget2, Andrea Stroux3, Cornelia Schlee1, Max Mossner1, Thomas Burmeister1, Stefan Schwartz1, Clara D. Bloomfield4, Dieter Hoelzer2, Eckhard Thiel1, Wolf-Karsten Hofmann1

1 Charité, University Hospital Berlin, Campus Benjamin Franklin, Department of Hematology and Oncology, Berlin, Germany
2 University Frankfurt am Main, Department of Hematology and Oncology, Frankfurt/Main, Germany
3 Charité, University Hospital Berlin, Campus Benjamin Franklin, Department of Biostatistics and Clinical Epidemiology, Berlin, Germany
4 The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA

Correspondence: Claudia D Baldus, M.D., Charité, University Hospital Berlin, Campus Benjamin Franklin, Department of Hematology and Oncology, Hindenburgdamm 30 12203 Berlin, Germany. E-mail:claudia.baldus{at}charite.de

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.

Key words: acute T-lymphoblastic leukemia, NOTCH1, FBXW7, mutations.


Related Article

Mutations of NOTCH1, FBXW7, and prognosis in T-lineage acute lymphoblastic leukemia
Charles G. Mullighan
Haematologica 2009 94: 1338-1340. [Full Text] [PDF]



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C. G. Mullighan
Mutations of NOTCH1, FBXW7, and prognosis in T-lineage acute lymphoblastic leukemia
Haematologica, October 1, 2009; 94(10): 1338 - 1340.
[Full Text] [PDF]