Psoralen with Ultraviolet A-induced Apoptosis of Cutaneous Lymphoma Cell Lines is Augmented by Type I Interferons Via the JAK1-STAT1 Pathway

Background: Photochemotherapy with psoralen and ultraviolet A (PUVA), with or without adjuvant interferon-α (IFN-α), is a first-line therapy for early-stage mycosis fungoides and other forms of cutaneous T-cell lymphoma (CTCL). However, the mechanism by which PUVA with IFN-α work in CTCL is poorly understood.

Purpose: To develop a model to investigate the mechanisms of PUVA and PUVA with IFN-α in CTCL cells.

Methods: An in vitro model to study the molecular mechanisms of PUVA was created using two different CTCL cell lines, MyLa, which has functional p53, and HuT-78, in which p53 is inactivated due to a homozygous nonsense mutation.

Results: PUVA caused G2/M cell cycle block and apoptosis of MyLa and HuT-78 accompanied by increase in the expression of the mitochondrial pro-apoptotic genes Bax, BAK, and PUMA and a downregulation in anti-apoptotic Bcl-2. p53 was induced and c-Myc was repressed by PUVA, but neither were essential for PUVA-induced apoptosis. IFN-α augmented PUVA-induced apoptosis via the JAK1 pathway, and this activity could be inhibited by ruxolitinib.

Conclusion: PUVA induces p53-independent apoptosis in CTCL cell lines, and this process is augmented by type I interferons via the JAK1 pathway.