The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL

Moritz Otte, Johanna Stachelscheid, Markus Glaß, Linus Wahnschaffe, Qu Jiang, Waseem Lone, Aleksandr Ianevski, Tero Aittokallio, Javeed Iqbal, Michael Hallek, Stefan Hüttelmaier, Alexandra Schrader, Till Braun, Marco Herling

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease.

Original languageEnglish (US)
Article number2527
Issue number9
StatePublished - May 2023


  • STAT4
  • T-PLL
  • T-cell lymphoma
  • cell proliferation
  • leukemogenesis
  • miR-141
  • miR-200c

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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