Lecture entitled ‘Genomics and Epigenomics of T-PLL’ by prof. Reiner Siebert from Ulm University will take place on May 31, 2022.
T-cell prolymphocytic leukemia (T-PLL) is an aggressive T-cell malignancy with a leukemic presentation of mature T-cells. The cytogenetic hallmark of T-PLL is an inv(14)(q11q32)/t(14;14)(q11;q32) or, alternatively, t(X;14)(q28;q11) which lead to activation of the TCL1A and MTCP1 oncogenes through TCR enhancer hijacking. In the last 15 years, we performed a series of studies aiming at characterizing the genomic, epigenomic and transcriptomic landscape of T-PLL. Among others, by investigating the structure of the inv(14)/t(14;14) we tracked the putative cell-of-origin in T-PLL. We showed that the quite conserved pattern of chromosomal imbalances is associated with changes of gene expression and identified mutations recurrently activating the JAK/STAT pathway. Current studies focus on the peculiar pattern of epigenomic changes in T-PLL, its link to TCL1A activation, mechanisms of epigenomic deregulation conserved between human T-PLL and corresponding mouse models, investigation of candidate genes, miRNA expression analyses as well studies on the role of viral infection in T-PLL pathogenesis. The lecture will provide a comprehensive overview on the molecular events underlying T-PLL pathogenesis.