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

被引:60
作者
Baldus, Claudia D. [1 ]
Thibaut, Julia [1 ]
Goekbuget, Nicola [2 ]
Stroux, Andrea [3 ]
Schlee, Cornelia [1 ]
Mossner, Max [1 ]
Burmeister, Thomas [1 ]
Schwartz, Stefan [1 ]
Bloomfield, Clara D. [4 ]
Hoelzer, Dieter [2 ]
Thiel, Eckhard [1 ]
Hofmann, Wolf-Karsten [1 ]
机构
[1] Univ Hosp Berlin, Charite, Dept Hematol & Oncol, D-12203 Berlin, Germany
[2] Goethe Univ Frankfurt, Dept Hematol & Oncol, Frankfurt, Germany
[3] Univ Hosp Berlin, Charite, Dept Clin Epidemiol & Biostat, D-12203 Berlin, Germany
[4] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
来源
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2009年 / 94卷 / 10期
关键词
acute T-lymphoblastic leukemia; NOTCH1; FBXW7; mutations; TUMOR-SUPPRESSOR; STANDARD-RISK; HUMAN HOMOLOG; CELL-CYCLE; EXPRESSION; RESISTANCE; GENE; INACTIVATION; ACTIVATION; ERG;
D O I
10.3324/haematol.2008.005272
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 over-all 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
引用
收藏
页码:1383 / 1390
页数:8
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