ASH 2025 | Intronic DNA variants in EZH2 and GATA2 may predict TFR in CML
Shaun Patterson, PhD, University of Glasgow, Glasgow, UK, shares insights into the DESTINY trial (NCT01804985), which investigated the discontinuation of TKIs in patients with chronic myeloid leukemia (CML). He states that intronic DNA variants, including EZH2 and GATA2, may predict treatment-free remission (TFR), and further suggests that these findings could be validated in a larger prospective clinical trial to potentially improve patient stratification and quality of life. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So the work we’ve done is on the DESTINY clinical trial which was a multi-center trial in the UK looking at CML patients who were discontinuing TKI and so we’ve looked at the bone marrow of these patients at the start of the trial at the point of their de-escalation and found that in the DNA of those cells there are a number of intronic DNA variants that we think might be predictive of treatment-free remission...
So the work we’ve done is on the DESTINY clinical trial which was a multi-center trial in the UK looking at CML patients who were discontinuing TKI and so we’ve looked at the bone marrow of these patients at the start of the trial at the point of their de-escalation and found that in the DNA of those cells there are a number of intronic DNA variants that we think might be predictive of treatment-free remission. That’s at the end point of the trial and so we think this could translate into maybe a larger prospective clinical trial in order to validate these results. So we worked with the NHS in Glasgow on this, their genomics facility. We isolated DNA from the bone marrow mononuclear cells from these patients and ran this through the clinical pipeline using a 56 gene panel. And we have looked at the variant allele frequency for each of those genes, called at 5%, and then produced a list of variants of interest. And so when we put these together in multi-parameter logistic regression, we found that there was the EZH2 and the GATA2 variants of interest that we think might be predictive. As I say, this needs to be validated in another cohort. So this potentially could be used for patients who present at the clinic. They’re being seen as similar patients and they’re under consideration for TFR. Other parameters say that they are eligible but this could actually help to stratify patients further and improve the risk profile of stopping or discontinuing their TKI. Potentially if we’re able to incorporate other markers such as BCR-ABL level it may be used to stratify patients into further subgroups. So at the moment it’s difficult to say exactly how it could be used, but it could really improve quality of life for patients, not just by stopping their TKI, but also by improving the anxiety that is faced by patients having to make that decision.
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