There is increasing recognition of the risk of developing therapy-related myeloid malignancy, including after cellular therapy. While retrospective studies have implicated pre-existing TP53 mutated hematopoietic clones as a common causative mechanism, no prospective screening to identify those patients at greatest risk is currently possible. We demonstrate that ultradeep DNA-sequencing prior to therapy may be used for discovery of TP53 mutations that are subsequently associated with malignancy.

Research at the Laboratory of Myeloid Malignancies, NHLBI is supported by the Foundation of the NIH AML MRD Biomarkers Consortium. The authors declare no other competing interests.

This work was funded by the Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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A part of the current study includes human data that were originally published as: Ghannam, J.Y., Xu, X., Maric, I., Dillon, L., Li, Y., Hsieh, M.M., Hourigan, C.S. and Fitzhugh, C.D., 2020. Baseline TP53 mutations in adults with SCD developing myeloid malignancy following hematopoietic cell transplantation. Blood, The Journal of the American Society of Hematology, 135(14), pp.1185-1188. https://ashpublications.org/blood/article/135/14/1185/452511/Baseline-TP53-mutations-in-adults-with-SCD

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