Activation of the TCL1 oncogene is arguably one of most studied initiating events in the pathogenesis of aggressive CLL. TCL1 (T cell leukemia/lymphoma 1) was first identified as a target of translocations and inversions at 14q32.1, common chromosomal aberrations in T-cell prolymphocytic leukemias [28]. Expression analyses of TCL1 revealed that this gene is mostly expressed in B-cells and to a much lesser extent in T-cells [28]. In B-cells, Tcl1 is expressed in all stages of development, except mature B-cells [29, 30]. Since our study demonstrating that TCL1 deregulation in mouse B-cells results in aggressive CLL [31], several additional reports have indicated that Tcl1 is critical molecule in the CLL pathogenesis [13, 32]. Importantly, high Tcl1 expression in human CLL correlates with aggressive CLL phenotype showing unmutated immunoglobulin variable region genes and ZAP70 positivity [32].
