Hemato · Published 2026-06-08 · DOI 10.3390/hemato7020021
Ahmed S. Mohamed, Marina Basta, Shibhani Rajanna, Maggie James, Ashrakat Deyab, Shareif Abdelwahab, Umang Gupta, Simcha Weissman
We report a female in her late 80s with high-risk pleomorphic mantle cell lymphoma (MCL) harboring germline <i>ATM</i> mutation and 17p deletion who achieved complete metabolic response with zanubrutinib plus rituximab. Serial peripheral blood next-generation sequencing (NGS) during remission revealed emergence of a molecularly distinct pre-leukemic clone characterized by <i>DNMT3A</i>, <i>TET2</i>, and a <i>TP53</i> point mutation (p.Tyr220Cys)—distinct from the original 17p deletion. Approximately 20 months after MCL diagnosis, she developed acute myeloid leukemia (AML) with <i>FLT3</i>-TKD and <i>NPM1</i> mutations, confirming transformation of the pre-leukemic clone. Longitudinal VAF tracking demonstrated complete eradication of MCL-associated mutations (<i>ID3</i>, <i>BIRC3</i>) while the myeloid clone expanded. This case provides direct molecular evidence that AML arose from clonal evolution of a pre-existing hematopoietic clone rather than direct MCL transformation, with implications for understanding second malignancies in BTK inhibitor-treated patients.
Abstract from DOAJ. Public domain (CC0 1.0).
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Mohamed, A., Basta, M., Rajanna, S., et al. (2026). Acute Myeloid Leukemia Following Mantle Cell Lymphoma: Clonal Evolution Versus Therapy-Related Pathogenesis—A Case Report with Longitudinal Molecular Tracking. Hemato. https://doi.org/10.3390/hemato7020021