Aberrant expression of BCL11B in mycosis fungoides and its potential role in interferon‐induced apoptosis

Abstract

BCL11B is a Kruppel-like C2H2-type zinc finger transcription factor, which has been associated with several human malignancies. Recent evidence showed that overexpressed BCL11B conferred chemoresistance to malignant T cells and that inhibiting BCL11B led to increased apoptosis, suggesting its potential pathogenic relevance in cutaneous T-cell lymphomas (CTCL), which were characterized by the resistance to chemotherapy-induced apoptosis. To investigate the expression pattern of BCL11B in different stages of mycosis fungoides (MF), quantitative reverse transcription polymerase chain reaction and immunohistochemistry were performed to compare the mRNA and protein expression among different stages of MF and benign inflammatory dermatoses (BID), respectively. BCL11B demonstrated significant upregulation in all stages of MF, compared with BID, in both mRNA expression level and protein level. In addition, BCL11B expression increased with advancing lesion tumor stage and overall disease stage. Further, to evaluate the dynamic expression of BCL11B under CTCL-directed treatment, BCL11B expression and cell apoptosis were evaluated after interferon (IFN)-α-2b and methotrexate treatment on CTCL cell line Hut78 cells. IFN-α-2b, but not methotrexate, induced BCL11B inhibition and cell apoptosis, suggesting that BCL11B may play important roles in the anti-CTCL effect of IFN-α-2b. In conclusion, our study demonstrated the overexpression of BCL11B in MF lesions and its potential relevance to disease progression. In addition, we provided evidence for BCL11B inhibitory approaches as a potential treatment to target chemoresistant tumor cells in advanced MF.

Commentary about papular mycosis fungoides, lymphomatoid papulosis and lymphomatoid pityriasis lichenoides: more similarities than differences

“…initiation) that favors clonal expansion in the environment of the skin, but by itself is insufficient to induce ‘malignant’ transformation. These would encompass the abortive and latent lymphoma categories including LyP that were proposed by Burg et al The specific molecular alteration (mutation) that might account for the initiation event is unknown, but possible candidates would be genes that impair normal lymphocyte apoptosis, leading to abnormal accumulation of T cells …”

New aspects of the clinicopathological features and treatment of mycosis fungoides and Sézary syndrome

“…22 It has been proposed that the accumulation of neoplastic cells over time depends on the resistance to apoptosis rather than the enhanced proliferation in MF. 23 In line with this notion, Gu et al demonstrated that BCL11B, an apoptosis resistance transcription factor, is overexpressed in MF compared with benign inflammatory skin diseases. In addition, the tumor progression is significantly correlated with the percentage expression of BCL11B ( Fig.…”

“…In addition, the tumor progression is significantly correlated with the percentage expression of BCL11B (Fig. ) …”

“…Decreases in the IFN‐γ‐producing Th1 milieu may potentiate the tumor progression of MF because IFN‐γ exerts antitumoral activity in MF . It has been proposed that the accumulation of neoplastic cells over time depends on the resistance to apoptosis rather than the enhanced proliferation in MF . In line with this notion, Gu et al .…”

“…1). 23 miRNA are short non-coding RNA molecules that regulate gene expression and contribute to biological processes including apoptosis, cell cycle progression and differentiation. To date, nearly 2500 miRNA have been found in humans.…”