Clinical and biological features of PTPN2-deleted adult and pediatric T-cell acute lymphoblastic leukemia.
Adolescent
Adult
Alleles
Biomarkers, Tumor
Female
Gene Frequency
Genotype
High-Throughput Nucleotide Sequencing
Humans
Immunophenotyping
Interleukin-7 Receptor alpha Subunit
/ genetics
Janus Kinases
/ metabolism
Male
Middle Aged
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
/ diagnosis
Prognosis
Protein Tyrosine Phosphatase, Non-Receptor Type 2
/ deficiency
STAT Transcription Factors
/ metabolism
Sequence Deletion
Young Adult
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
09 07 2019
09 07 2019
Historique:
received:
20
11
2018
accepted:
06
05
2019
entrez:
5
7
2019
pubmed:
5
7
2019
medline:
10
7
2020
Statut:
ppublish
Résumé
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% (
Identifiants
pubmed: 31270080
pii: bloodadvances.2018028993
doi: 10.1182/bloodadvances.2018028993
pmc: PMC6616254
doi:
Substances chimiques
Biomarkers, Tumor
0
IL7R protein, human
0
Interleukin-7 Receptor alpha Subunit
0
STAT Transcription Factors
0
Janus Kinases
EC 2.7.10.2
PTPN2 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 2
EC 3.1.3.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1981-1988Informations de copyright
© 2019 by The American Society of Hematology.
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