Leukemic forms of cutaneous T-cell lymphomas (L-CTCL) are aggressive lymphoproliferative disorders of mature T-cells in the skin causing chronic inflammation, tissue destruction, sepsis and metastasis, linked to high mortality. Despite many comprehensive sequencing studies, driver mutations remain unclear, but chromosomal losses and gains are frequent and dominant. Cancer genome landscape analysis is integrated with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. Along with other aims the immunomodulatory effect of phototherapy is assessed in clinical and pre-clinical CTCL models.