Key regulatory roles of PRDM1 in human NK-cell differentiation and activation
LEUKEMIA, vol.40, no.1, pp.199-210, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 40 Issue: 1
- Publication Date: 2026
- Doi Number: 10.1038/s41375-025-02815-z
- Journal Name: LEUKEMIA
- Journal Indexes: Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, EMBASE, MEDLINE
- Page Numbers: pp.199-210
- Dokuz Eylül University Affiliated: Yes
Abstract
PRDM1, encoding a transcription factor (TF), regulates plasma cell and CD8+ T-cell terminal differentiation and Th2 lineage specification, while its role in human NK-cell differentiation and homeostasis is largely unknown. Here, we employed a multi-omics approach to dissect the transcriptional control of PRDM1 on human NK-cells. PRDM1 is important in NK-cell terminal differentiation based on gene expression profiling and its targeting of key regulators in the process. PRDM1-deleted NK-cells displayed a less mature phenotype simulating the CD56bright NK-cell population accompanied by upregulation of stem-like gene signatures. PRDM1-bound genes were enriched in T/NK-cell receptor signaling, activation, and NK-cell effector functions. PRDM1 could function as a transcriptional repressor as well as an activator as its activities may be modified by association with different TFs and co-factors. The kinetics of its action also varies among its target genes. As a homeostatic factor, PRDM1 is induced upon IL-2 and feeder cell stimulation, but its ability to restrict NK-cell growth upon feeder stimulation may be counteracted by the AP-1-induced transcriptional network. The loss of PRDM1 activity is frequent in NK-cell malignancies which may lead to decreased homeostatic control, impaired terminal differentiation, enhanced cellular fitness, and the acquisition of more stem-like features, thereby promoting lymphomagenesis.