Browse by author
Lookup NU author(s): Dr Sarah Jenkinson, Professor Anthony MoormanORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Activating mutations in the NOTCH1 pathway are frequent in pediatric T-cell acute lymphoblastic leukemia (T-ALL) but their role in refining risk stratification is unclear. We screened 162 pediatric T-ALL patients treated on the MRC UKALL2003 trial for NOTCH1/FBXW7 gene mutations and related genotype to response to therapy and long-term outcome. Overall, 35% were wild-type (WT) for both genes (NOTCH1(WT)FBXW7(WT)), 38% single NOTCH1 mutant (NOTCH1(Single)FBXW7(WT)), 3% just FBXW7 mutant (NOTCH1(WT)FBXW7(MUT)) and 24% either double NOTCH1 mutant (NOTCH1(Double)FBXW7(WT)) or mutant in both genes (NOTCH1(MUT)FBXW7(MUT)), hereafter called as NOTCH1 +/- FBXW7(Double). There was no difference between groups in early response to therapy, but NOTCH1 +/- FBXW7(Double) patients were more likely to be associated with negative minimal residual disease (MRD) post-induction than NOTCH1(WT)FBXW7(WT) patients (71% versus 40%, P=0.004). Outcome improved according to the number of mutations, overall survival at 5 years 82%, 88% and 100% for NOTCH1(WT)FBXW7(WT), NOTCH1(Single)FBXW7(WT) and NOTCH1 +/- FBXW7(Double) patients, respectively (log-rank P for trend = 0.005). Although 14 NOTCH1 +/- FBXW7(Double) patients were classified as high risk (slow response and/or MRD positive), only two had disease progression and all remain alive. Patients with double NOTCH1 and/or FBXW7 mutations have a very good outcome and should not be considered for more intensive therapy in first remission, even if slow early responders or MRD positive after induction therapy. Leukemia (2013) 27, 41-47; doi:10.1038/leu.2012.176
Author(s): Jenkinson S, Koo K, Mansour MR, Goulden N, Vora A, Mitchell C, Wade R, Richards S, Hancock J, Moorman AV, Linch DC, Gale RE
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2013
Volume: 27
Issue: 1
Pages: 41-47
Print publication date: 01/01/2013
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/leu.2012.176
DOI: 10.1038/leu.2012.176
Altmetrics provided by Altmetric
