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Prognostic Implications of Mutations in NOTCH1 and FBXW7 in Childhood T-ALL Treated According to the NOPHO ALL-1992 and ALL-2000 Protocols
University of Gothenburg, Sweden .
University of Gothenburg, Sweden .
University of Gothenburg, Sweden .
University of Gothenburg, Sweden .
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2014 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 61, no 3, 424-430 p.Article in journal (Refereed) Published
Abstract [en]


In children, T-cell acute lymphoblastic leukemia (T-ALL) has inferior prognosis compared with B-cell precursor ALL. In order to improve survival, individualized treatment strategies and thus risk stratification algorithms are warranted, ideally already at the time of diagnosis.


We analyzed the frequency and prognostic implication of mutations in NOTCH1 and FBXW7 in 79 cases of Swedish childhood T-ALL treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL-1992 and ALL-2000 protocols. In a subgroup of patients, we also investigated the functional relevance of NOTCH1 mutations measured as expression of the HES1, MYB, and MYC genes.


Forty-seven of the cases (59%) displayed mutations in NOTCH1 and/or FBXW7. There was no difference in overall (P = 0.14) or event-free survival (EFS) (P = 0.10) in patients with T-ALL with mutation(s) in NOTCH1/FBXW7 compared with patients with T-ALL without mutations in any of these genes. T-ALL carrying NOTCH1 mutations had increased HES1 and MYB mRNA expression (HES1 9.2 ± 1.9 (mean ± SEM), MYB 8.7 ± 0.8 (mean ± SEM)) compared to T-ALL with wild-type NOTCH1 (HES1 1.8 ± 0.7, MYB 5.1 ± 1.2, P = 0.02 and 0.008, respectively). In cases of T-ALL with high HES1 expression, improved overall (P = 0.02) and EFS (P = 0.028) was seen.


Increased NOTCH activity, reflected by increased HES1 expression, is associated with improved outcome in pediatric T-ALL, but its role as a diagnostic tool or a therapeutic target in future clinical treatment protocols remains to be elucidated. Pediatr Blood Cancer 2014;61:424–430.

Place, publisher, year, edition, pages
Wiley , 2014. Vol. 61, no 3, 424-430 p.
Keyword [en]
cytogenetics and molecular genetics; FBXW7; NOTCH1; pediatric acute lymphoblastic leukemia; prognosis
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-104279DOI: 10.1002/pbc.24803ISI: 000329585300006OAI: diva2:697208
Available from: 2014-02-17 Created: 2014-02-14 Last updated: 2014-02-21Bibliographically approved

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Department of Paediatrics in Linköping
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Pediatric Blood & Cancer
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