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Title

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

Authors
Alcantara, Marion
Simonin, Mathieu
Lhermitte, Ludovic
Touzart, Aurore
Dourthe, Marie Emilie
Latiri, Mehdi
Grardel, Nathalie
Cayuela, Jean Michel
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Published in Blood Advances. 2019, vol. 3, no. 13, p. 1981-1988
Abstract 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).
Keywords AdolescentAdultAllelesBiomarkers, TumorFemaleGene FrequencyGenotypeHigh-Throughput Nucleotide SequencingHumansImmunophenotypingInterleukin-7 Receptor alpha Subunit/genetics/metabolismJanus Kinases/metabolismMaleMiddle AgedPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics/mortality/therapyPrognosisProtein Tyrosine Phosphatase, Non-Receptor Type 2/deficiencySTAT Transcription Factors/metabolismSequence DeletionYoung Adult
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PMID: 31270080
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Research group Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982)
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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 https://archive-ouverte.unige.ch/unige:143934

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Deposited on : 2020-11-02

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