New Study Uses Targeted NGS to Track Therapy Resistance in MCL
Mantle cell lymphoma (MCL) is a rare but aggressive blood cancer that often responds to advanced treatments at first. Over time, however, many patients develop resistance to therapies like BTK inhibitors (BTKi) and venetoclax, leaving clinicians with fewer options.
A newly published study in The Journal of Pathology sheds light on the genetic reasons behind this resistance, and we’re proud that Paragon Genomics’ CleanPlex TP53 Panel played a key role in the discovery.
What the Study Explored
Researchers analyzed tumor samples from 8 MCL patients who had been treated with both BTKi and venetoclax. Their goal: to understand the genetic evolution of the cancer, and how it managed to survive both therapies.
They used a combination of:
Low-coverage whole-genome sequencing to map broad DNA changes CleanPlex® TP53 Panel to precisely detect mutations in the TP53 gene, a key regulator of cell death
What They Found
Resistant cancers had more DNA changes, especially after therapy.
BTKi-resistant tumors often had mutations in genes like NOTCH1, TRAF2, and ATM.
Venetoclax-resistant tumors frequently lost a segment of chromosome 9 (9p21.3), which houses tumor-suppressing genes.
One patient showed a clear pattern of clonal evolution, with new genetic mutations emerging over time — a hallmark of treatment resistance.
How CleanPlex Made an Impact
The CleanPlex® TP53 Panel enabled:
- Accurate detection of TP53 mutations, even in small subclones
- High-depth, targeted sequencing from limited material
- Longitudinal tracking of clonal changes throughout therapy
This helped researchers piece together how the cancer evolved and which mutations may have contributed to treatment failure, offering new insights into future therapeutic strategies.
Why This Matters
Understanding genetic resistance mechanisms can guide more personalized cancer treatment. With tools like CleanPlex, researchers and clinicians can gain earlier insights into therapy response and adapt treatment plans accordingly.
We’re honored to support groundbreaking research that brings us closer to smarter, more precise cancer care.
Read the full study: Resistance mechanisms and clonal dynamics in mantle cell lymphoma treated with sequential BTKi and venetoclax therapy
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