4.5 Article

High Expression of IKZF2 in Malignant T Cells Promotes Disease Progression in Cutaneous T Cell Lymphoma

Journal

ACTA DERMATO-VENEREOLOGICA
Volume 101, Issue -, Pages -

Publisher

ACTA DERMATO-VENEREOLOGICA
DOI: 10.2340/actadv.v101.570

Keywords

cutaneous T cell lymphoma; IKZF2; apoptosis; PD-1; interleukin-10

Categories

Funding

  1. National Nature Science Foundation of China [81872214, 81922058]
  2. National Youth Top-Notch Talent Support Program
  3. Peking University Medical Cross Research Seed Fund

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Cutaneous T cell lymphoma is a chronic disease that can exhibit aggressive behavior in advanced stages, leading to poor prognosis. The transcription factor IKZF2 is found to be overexpressed in malignant T cells, particularly in advanced-stage lesions, promoting disease progression by inhibiting cell apoptosis and potentially contributing to tumor immune evasion.
Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, cutaneous T cell lymphoma may manifest aggressive clinical behaviour and lead to a poor prognosis. The mechanism of disease progression in cutaneous T cell lymphoma remains unknown. This study, based on a large clinical cohort, found that IKZF2, an essential transcription factor during T cell development and differentiation, showed stage-dependent overexpression in the malignant T cells in mycosis fungoides lesions. IKZF2 is specifically over-expressed in advanced-stage mycosis fungoides lesions, and correlates with poor prognosis. Mechanistically, overexpression of IKZF2 promotes cutaneous T cell lymphoma progression via inhibiting malignant cell apoptosis and may contribute to tumour immune escape by downregulating major histocompatibility complex II molecules and up-regulating the production of anti-inflammatory cytokine interleukin-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk cutaneous T cell lymphoma and pave the way for future targeted therapy.

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