“…Historically, mature T cells were presumed to be the targets for transformation, based on gene expression profiling and the presence of surface markers such as CD4 or CD30, as well as production of cytotoxic proteins such as Granzyme B and Perforin (Benharroch et al, 1998; Eckerle et al, 2009; Swerdlow et al, 2008). However, ALK+ cells are present in stem cell-enriched cord blood, and a study has identified a side population of cells in ALK+ ALCL cell lines and tumors with signatures similar to early thymic progenitors (ETPs), suggesting that transformation of T cells by NPM-ALK might occur early during thymic T cell development (Laurent et al, 2012; Moti et al, 2015). Subsequently, a mechanism has been proposed whereby in a murine mimic of ALK+ ALCL transient expression of a functional TCR is required for thymic emigration of incipient, thymic-resident tumor cells, but the TCR is then downregulated for peripheral lymphomagenesis (Malcolm et al, 2016).…”