Summary
A bioRxiv preprint reports that changes involving DNMT1 can reduce CTCF binding at the KMT2A gene and promote copy gains and rearrangements. The findings come from experimental molecular research, not a clinical study.
A bioRxiv preprint reports experimental evidence that epigenetic changes involving DNMT1 can make the KMT2A gene more susceptible to copy gains and rearrangements. The authors link these changes to reduced occupancy of CTCF, a protein involved in organising genome structure. The work is molecular research; the abstract does not describe a clinical study.
How the researchers linked methylation to KMT2A changes
The authors report that rapidly degrading CTCF produced local changes in genome structure around KMT2A, alongside gene copy gains and rearrangements. They also found that increasing DNMT1 was associated with more H3K9 methylation, less CTCF occupancy at the locus and KMT2A alterations. DNA methylation and H3K9 methylation are chemical modifications that can affect how DNA is packaged and regulated.
In a further intervention, inhibiting DNMT1 suppressed KMT2A alterations caused by topoisomerase II inhibition. The researchers also used locus-specific epigenome targeting: promoting DNA or H3K9 methylation at KMT2A increased copy gains and rearrangements, while targeted TET activity suppressed these events after methylation perturbation or doxorubicin treatment.
What the findings could mean
KMT2A amplifications and rearrangements occur in infant and adult leukaemia, as well as in some therapy-associated cases, according to the preprint. Amplification means a gene has additional copies; rearrangement means its DNA has been structurally altered. The reported experiments suggest that the methylation state around KMT2A may help shape its susceptibility to these changes, rather than the locus being affected only by genome damage.
The authors propose that this DNA-and-histone methylation pathway could point to biomarkers or ways to intercept KMT2A alterations. Those are research directions, not established clinical applications. The findings are reported in a bioRxiv preprint, and its available abstract does not specify the experimental models or sample sizes, limiting assessment of how broadly the results apply.