Clinical and biological features of PTPN2-deleted adult and pediatric T-cell acute lymphoblastic leukemia.
(2019) Blood Advances — Vol. 3, n° 13, p. 1981-1988 (2019)
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- 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% ( = .177).
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Alcantara, M., Simonin, M., Lhermitte, L., Touzart, A., Dourthe, M. E., Latiri, M., Grardel, N., Cayuela, J. M., Chalandon, Y., Graux, C., Dombret, H., Ifrah, N., Petit, A., Macintyre, E., Baruchel, A., Boissel, N., & Asnafi, V. (2019). Clinical and biological features of PTPN2-deleted adult and pediatric T-cell acute lymphoblastic leukemia. Blood Advances, 3(13), 1981-1988. https://doi.org/10.1182/bloodadvances.2018028993 (Original work published 2019)