student research day - Case Western Reserve University School of ...

Min Deng
Bcl-2 photodamage and preferential killing of malignant T cells after photodynamic therapy of
mycosis fungoides, using silicon phthalocyanine Pc 4
Deng M, Lam M, Hsia A, Baron E
Dermatology Department, University Hospitals of Case Western Reserve School of Medicine
Key Words: Cutaneous T-cell Lymphoma, Photodynamic Therapy, Pc4, Bcl-2, CD45RB, CD45RO
Mycosis Fungoides is a primary cutaneous T-cell lymphoma characterized by malignant epidermotrophic-T-cells that are
largely CD45RB+ and CD45RO-. In vitro studies using photodynamic therapy with silicon phthalocyanine Pc 4 indicated
increased sensitivity of Jurkat T-cells to PDT-induced killing. The mechanism behind Pc 4-PDT cell killing is known to involve
photodamage to the anti-apoptotic protein bcl-2. The purpose of this study was to evaluate skin biopsies from MF patients
treated with Pc 4-PDT for damage to bcl-2 and preferential killing of malignant T cells. From a Phase 1 clinical trial on Pc 4-
PDT, tissue samples of treated and untreated MF lesions were available from 6 patients who clinically demonstrated partial
response. These biopsies were evaluated for bcl-2 expression via Western blot. Paraffin sections from the biopsies were
likewise stained with antibodies to CD45RB and CD45RO, and assessed via image analysis (Image Pro Plus, Media
Cybernetics). T-testing was used to determine statistical significance. Bcl-2 expression in treated lesions collected from
patients who showed clinical response was significantly decreased when compared to untreated lesions. Interestingly, bcl-2
expression in treated lesions collected from patients who did not respond clinically was not different from untreated
lesions. CD45RB-stained surface area was significantly reduced in treated lesions compared to corresponding untreated
lesions (p=0.0078). Treated lesions stained with CD45RO showed marginal significance upon Pc 4-PDT (p=0.056). On
average, the reduction of CD45RB was 2.1 times higher than the reduction of CD45RO. The ratio of reduction of CD45RB to
CD45RO was marginally significant (p=0.069). Patients who clinically responded to Pc 4-PDT showed molecular evidence of
Bcl-2 damage that was not seen in patients who did not respond to treatment. Although there was reduction in both T-cell
markers, CD45RB and CD45RO, the more pronounced reduction of CD45RB compared to reduction of CD45RO suggests a
trend that shows a more sensitive effect on epidermal malignant T-cells vs. benign reactive T-cells.
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