Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia

• Verfasst von: López, Cristina [VerfasserIn]
• Verfasst von: Bergmann, Anke K. [VerfasserIn]
• Verfasst von: Paul, Ulrike [VerfasserIn]
• Verfasst von: Penas, Eva M. Murga [VerfasserIn]
• Verfasst von: Nagel, Inga [VerfasserIn]
• Verfasst von: Betts, Matthew J. [VerfasserIn]
• Verfasst von: Johansson, Patricia [VerfasserIn]
• Verfasst von: Ritgen, Matthias [VerfasserIn]
• Verfasst von: Baumann, Tycho [VerfasserIn]
• Verfasst von: Aymerich, Marta [VerfasserIn]
• Verfasst von: Jayne, Sandrine [VerfasserIn]
• Verfasst von: Russell, Robert B. [VerfasserIn]
• Verfasst von: Campo, Elias [VerfasserIn]
• Verfasst von: Dyer, Martin JS [VerfasserIn]
• Verfasst von: Dürig, Jan [VerfasserIn]
• Verfasst von: Siebert, Reiner [VerfasserIn]
• Titel: Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia
• Verf.angabe: Cristina López, Anke K. Bergmann, Ulrike Paul, Eva M. Murga Penas, Inga Nagel, Matthew J. Betts, Patricia Johansson, Matthias Ritgen, Tycho Baumann, Marta Aymerich, Sandrine Jayne, Robert B. Russell, Elias Campo, Martin JS Dyer, Jan Dürig and Reiner Siebert
• E-Jahr: 2016
• Jahr: 25 February 2016
• Umfang: 9 S.
• Fussnoten: Gesehen am 18.05.2020
• Titel Quelle: Enthalten in: British journal of haematology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1955
• Jahr Quelle: 2016
• Band/Heft Quelle: 173(2016), 2, Seite 265-273
• ISSN Quelle: 1365-2141
• DOI: doi:10.1111/bjh.13952
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: epigenetic regulators
• Sach-SW: JAK3
• Sach-SW: STAT5B
• Sach-SW: T-cell lymphoma
• Sach-SW: T-cell prolymphocytic leukaemia
• K10plus-PPN: 169845628X

Abstract

T-cell prolymphocytic leukaemia (T-PLL) is an aggressive leukaemia. The primary genetic alteration in T-PLL are the inv(14)(q11q32)/t(14;14)(q11;q32) leading to TRD/TRA-TCL1A fusion, or the t(X;14)(q28;q11) associated with TRD/TRA-MTCP1 fusion. However, additional cooperating abnormalities are necessary for emergence of the full neoplastic phenotype. Though the pattern of secondary chromosomal aberrations is remarkably conserved, targets of the changes are largely unknown. We analysed a cohort of 43 well-characterized T-PLL for hotspot mutations in the genes JAK3, STAT5B and RHOA. Additionally, we selected a subset of 23 T-PLL cases for mutational screening of 54 genes known to be recurrently mutated in T-cell and other haematological neoplasms. Activating mutations in the investigated regions of the JAK3 and STAT5B genes were detected in 30% (13/43) and 21% (8/39) of the cases, respectively, and were mutually exclusive. Further, we identified mutations in the genes encoding the epigenetic regulators EZH2 in 13% (3/23), TET2 in 17% (4/23) and BCOR in 9% (2/23) of the cases. We confirmed that the JAK-STAT pathway is a major mutational target, and identified epigenetic regulators recurrently mutated in T-PLL. These findings complement the mutational spectrum of secondary aberrations in T-PLL and underscore the potential therapeutical relevance of epigenetic regulators in T-PLL.