Cutaneous T-Cell Lymphoma: Yin-Yang Effects of Transcription Factors HLF and NFIL3 in Regulation of Malignant T-cell Markers in the Context of HDAC Inhibitor Romidepsin Treatment

The drug romidepsin which is known to regulate gene expression has been shown to be an effective treatment in a subset of patient with cutaneous T-cell lymphoma (CTCL). We examined changes in gene expression that occurred through repeated romidepsin treatments using carefully collected blood cell samples from treated CTCL patients. Focusing on data from highly responsive CTCL patient through 12 months of treatment, including a period free from disease, we identified new markers that are characteristic of the malignant cells and markers of difficult to detect residual disease. We have identified functional effect and potential mechanisms of dysregulation through miRNA and DNA methylation and found significant impact of regulators HLF (activator) and NFIL3 (suppressor) that control expression of a significant number of malignant cell markers. We report new surface markers for the malignant cells, including markers identifiable in residual disease, and new potential therapeutic targets.