# CDK9 Inhibition with enitociclib reveals influence on HERV and LINE RNA abundances in whole blood, T-, and B-Cell lines

## TL;DR

This study shows that CDK9 inhibition with enitociclib affects retroelement RNA levels in lymphocytes and lymphoma patients.

## Contribution

The novel finding is that CDK9 inhibition differentially regulates endogenous retroelement RNA expression in a time- and cell-specific manner.

## Key findings

- CDK9 inhibition upregulates endogenous retroelement RNA in T- and B-cell lines.
- ERE activity in patients initially decreases but then increases before returning to baseline.
- EREs show differential sensitivity to CDK9 inhibition, indicating complex interactions with P-TEFb.

## Abstract

Endogenous retroelements (EREs) comprise a significant portion of the human genome and there is a growing appreciation for their roles in eukaryotic physiology. In lymphomas, EREs may contribute to proto-oncogene expression and their RNA expression can be useful to better define lymphoma sub-classifications. Several emerging cancer therapies suggest that targeting ERE expression may even be beneficial to patient outcome. In this study, we investigated how enitociclib, a CDK9 inhibitor, impacted ERE expression over time. Using in vitro models of T and B lymphocytes, we found that CDK9 inhibition upregulates transcriptional abundances of ERE RNAs in a cell type- and temporal- specific manner. Leveraging this data with data collected from a retrospective cohort of patients with lymphomas receiving enitociclib, we found that ERE activity was initially downregulated, followed by a substantial upregulation in expression before a return to baseline expression levels within forty-eight hours. These results showed that ERE activity is differentially sensitive to CDK9 inhibition and highlights the complexity of interactions between the P-TEFb complex and nascent ERE RNAs.

The online version contains supplementary material available at 10.1186/s12920-026-02309-6.