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Patient-Specific Circulating Tumor DNA for Monitoring Response to Menin Inhibitor Treatment in Preclinical Models of Infant Leukemia. | LitMetric

Patient-Specific Circulating Tumor DNA for Monitoring Response to Menin Inhibitor Treatment in Preclinical Models of Infant Leukemia.

Cancers (Basel)

Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW 2052, Australia.

Published: November 2024

AI Article Synopsis

Article Abstract

Background: In infant ()-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), early relapse and treatment response are currently monitored through invasive repeated bone marrow (BM) biopsies. Circulating tumor DNA (ctDNA) in peripheral blood (PB) provides a minimally invasive alternative, allowing for more frequent disease monitoring. However, a poor understanding of ctDNA dynamics has hampered its clinical translation. We explored the predictive value of ctDNA for detecting minimal/measurable residual disease (MRD) and drug response in a patient-derived xenograft (PDX) model of infant MLL-r ALL.

Methods: Immune-deficient mice engrafted with three MLL-r ALL PDXs were monitored for ctDNA levels before and after treatment with the menin inhibitor SNDX-50469.

Results: The amount of ctDNA detected strongly correlated with leukemia burden during initial engraftment prior to drug treatment. However, following SNDX-50469 treatment, the leukemic burden assessed by either PB leukemia cells through flow cytometry or ctDNA levels through droplet digital polymerase chain reaction (ddPCR) was discrepant. This divergence could be attributed to the persistence of leukemia cells in the spleen and BM, highlighting the ability of ctDNA to reflect disease dynamics in key leukemia infiltration sites.

Conclusions: Notably, ctDNA analysis proved to be a superior predictor of MRD compared to PB assessment alone, especially in instances of low disease burden. These findings highlight the potential of ctDNA as a sensitive biomarker for monitoring treatment response and detecting MRD in infant MLL-r ALL.

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers16233990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11640178PMC

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