A proposed model of malignant dedifferentiation and TOX expression in CTCL.TOX and BLK become upregulated during thymic development of CD4⁺ T cells (left). In contrast, mature peripheral CD4⁺ T cells do not upregulate TOX on TCR stimulation and do not express BLK (middle). TOX- and BLK-positive malignant T-cell clones arise from a derailed thymic stem cell (dashed arrow) or as a result of TOX-dependent and/or TOX-independent dedifferentiation of malignant T cells or a precursor T cell (solid arrow). Dedifferentiation of the malignant T cell (or a precursor T cell) drives deregulated expression of transcription factors (including TOX), Scr kinases (including BLK), cytokines, and lymphangiogenic factor (right), leading to progressive disease and a mixed phenotype mimicking Th2, Th17, Th22, central memory/resident memory T cells (T_CM/T_RM), and LTi cells (right). Professional illustration by Luk Cox, Somersault 18:24.