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

Br J Haematol. 2016 Apr;173(2):265-73. doi: 10.1111/bjh.13952. Epub 2016 Feb 25.


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.

Keywords: JAK3; STAT5B; T-cell lymphoma; T-cell prolymphocytic leukaemia; epigenetic regulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Cohort Studies
  • DNA Mutational Analysis / methods
  • Epigenesis, Genetic / genetics*
  • Female
  • Genetic Markers / genetics
  • Humans
  • Janus Kinase 3 / genetics*
  • Leukemia, Prolymphocytic, T-Cell / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Proto-Oncogene Proteins / genetics
  • Recurrence
  • Repressor Proteins / genetics
  • STAT5 Transcription Factor / genetics*
  • Signal Transduction
  • rhoA GTP-Binding Protein / genetics


  • BCOR protein, human
  • Biomarkers, Tumor
  • Genetic Markers
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • STAT5 Transcription Factor
  • STAT5B protein, human
  • JAK3 protein, human
  • Janus Kinase 3
  • rhoA GTP-Binding Protein