Scientific article
Open access

Clinical and biological features of PTPN2-deleted adult and pediatric T-cell acute lymphoblastic leukemia

Published inBlood Advances, vol. 3, no. 13, p. 1981-1988
Publication date2019

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a phosphatase known to be a tumor suppressor gene in T-cell acute lymphoblastic leukemia (T-ALL). Because the full clinicobiologic characteristics of PTPN2 loss remain poorly reported, we aimed to provide a comprehensive analysis of PTPN2 deletions within a cohort of 430 patients, including 216 adults and 214 children treated according to the GRAALL03/05 (#NCT00222027 and #NCT00327678) and the FRALLE2000 protocols, respectively. We used multiplex ligation-dependent probe amplification to identify an 8% incidence of PTPN2 deletion, which was comparable in adult (9%) and pediatric (6%) populations. PTPN2 deletions were significantly associated with an αβ lineage and TLX1 deregulation. Analysis of the mutational genotype of adult T-ALL revealed a positive correlation between PTPN2 deletions and gain-of-function alterations in the IL7R/JAK-STAT signaling pathway as well as PHF6 and WT1 mutations. Of note, PTPN2 and PTEN (phosphatase and tensin homolog) deletions were mutually exclusive. Regarding treatment response, PTPN2-deleted T-ALLs were associated with a higher glucocorticoid response and a trend for improved survival in children, but not in adults, with a 5-year cumulative incidence of relapse of 8% for PTPN2-deleted pediatric cases vs 26% (P = .177).

  • Adolescent
  • Adult
  • Alleles
  • Biomarkers, Tumor
  • Female
  • Gene Frequency
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunophenotyping
  • Interleukin-7 Receptor alpha Subunit/genetics/metabolism
  • Janus Kinases/metabolism
  • Male
  • Middle Aged
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics/mortality/therapy
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2/deficiency
  • STAT Transcription Factors/metabolism
  • Sequence Deletion
  • Young Adult
Citation (ISO format)
ALCANTARA, Marion et al. Clinical and biological features of PTPN2-deleted adult and pediatric T-cell acute lymphoblastic leukemia. In: Blood Advances, 2019, vol. 3, n° 13, p. 1981–1988. doi: 10.1182/bloodadvances.2018028993
Main files (1)
Article (Published version)
Secondary files (1)
ISSN of the journal2473-9529

Technical informations

Creation10/28/2020 11:55:00 AM
First validation10/28/2020 11:55:00 AM
Update time03/15/2023 10:55:16 PM
Status update03/15/2023 10:55:15 PM
Last indexation01/17/2024 11:20:38 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack