The presence of mutated and deleted PTEN is associated with an increased risk of relapse in childhood T cell acute lymphoblastic leukaemia treated with AIEOP-BFM ALL protocols

Br J Haematol. 2018 Sep;182(5):705-711. doi: 10.1111/bjh.15449. Epub 2018 Jun 25.


Notwithstanding the improvement in treatment results for paediatric T cell acute lymphoblastic leukaemia (T-ALL) it remains important to understand if genetic aberrations influence therapy response. PTEN tumour suppressor gene inactivation is a frequent event in T-ALL but its effect on patient therapy response is debatable. We analysed the effect of the presence of mutated PTEN on outcome in 257 children with T-ALL treated with Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)-Berlin-Frankfürt-Münster (BFM) protocols. PTEN mutations were present in 31 (12·1%) patients and were significantly associated with increased risk of relapse. PTEN mutations also indicate a poor prognosis in T-ALL patients in the absence of NOTCH1 mutations or in the group of patients with co-presence of PTEN mutation and deletions. These results indicate that PTEN genomic aberrations and the biologically consequential PTEN inactivation contribute to adverse therapy response in T-ALL patients; PTEN status as a biomarker may contribute to the development of new molecularly-defined stratification algorithms.

Keywords: PTEN; T cel leukaemia; leukaemia; paediatric T-ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / therapeutic use
  • Child
  • Child, Preschool
  • Daunorubicin / therapeutic use
  • Female
  • Gene Deletion
  • Humans
  • Male
  • Mutation
  • PTEN Phosphohydrolase / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prednisone / therapeutic use
  • Prognosis
  • Recurrence
  • Vincristine / therapeutic use


  • Vincristine
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Asparaginase
  • Prednisone
  • Daunorubicin

Supplementary concepts

  • PVDA protocol