Acute myeloid leukaemia (AML) is one of the most aggressive and genetically complex cancers, marked by the unchecked growth of immature myeloid cells. Its diversity stems from numerous genetic alterations that disrupt normal blood cell development, presenting significant challenges in developing effective, universal therapies. While current treatments often target specific genetic abnormalities, they fall short of addressing the underlying transcriptional networks that sustain leukaemia. Uncovering shared vulnerabilities across AML subtypes has become a pressing priority to devise more inclusive and effective therapeutic strategies.

In a study (DOI: 10.1093/procel/pwae059) published on October 25, 2024, in the journal Protein & Cell, researchers from Tsinghua University and The Rockefeller University revealed an unprecedented role for JMJD1C in regulating gene expression in AML cells. By interacting with RUNX1, a critical transcription factor, JMJD1C drives leukaemia cell survival, making it a compelling therapeutic target. This discovery sheds light on how molecular mechanisms underpinning AML could be disrupted to combat this aggressive disease.

The research delves into how JMJD1C facilitates leukaemia cell survival by forming liquid-like condensates through its intrinsically disordered N-terminal region. This unique feature enables JMJD1C to be recruited by RUNX1 to genomic loci, including super-enhancers (SEs). These interactions activate key genes responsible for AML cell proliferation and metabolic processes, maintaining the leukaemic state. Importantly, the study highlights that JMJD1C’s non-catalytic functions are critical, with its condensate-forming ability being essential for RUNX1 recruitment and gene regulation.

Key experiments revealed that disrupting JMJD1C's N-terminal region impairs its ability to form condensates and interact with RUNX1, leading to reduced leukaemia cell viability. Moreover, JMJD1C’s RUNX1-containing condensates might mediate enhancer-promoter interactions crucial for the expression of key leukaemic genes regulated by RUNX1. These findings underscore the therapeutic potential of targeting the JMJD1C-RUNX1 axis to halt leukaemia progression.

Dr. Mo Chen, one of the senior authors of the study, highlighted the transformative potential of these findings: This research uncovers a previously unappreciated role for JMJD1C in leukaemia biology. By elucidating its interaction with RUNX1, we can now envision therapeutic strategies that target this axis across diverse AML subtypes.

The discovery of JMJD1C's role in AML cell survival opens a new frontier in leukaemia treatment. By targeting the JMJD1C-RUNX1 interaction, researchers hope to disrupt the transcriptional programs sustaining leukaemia cells, offering a universal strategy to tackle AML's heterogeneity. This approach holds promise for overcoming resistance to current therapies and improving patient outcomes. Future research will focus on translating these molecular insights into clinical interventions, heralding a new era in the fight against leukaemia.

References

DOI

10.1093/procel/pwae059

Original Source URL

https://doi.org/10.1093/procel/pwae059

About Protein & Cell

Protein & Cell is a fully open access, peer-reviewed journal that publishes research concerning the latest developments in multidisciplinary areas in biology and biomedicine, with an emphasis on protein and cell research. Subject areas include biochemistry, biophysics, cell biology, developmental biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology and translational medicine. In addition, Protein & Cell addresses research highlights, news and views, and commentaries covering research policies and funding trends in China, and provides a forum to foster academic exchange among researchers across different fields of the life sciences.