Clonal Dynamics and Relapse Risk Revealed by High-Sensitivity FLT3-Internal Tandem Duplication Detection in Acute Myeloid Leukemia.

Autor:	Oduro KA Jr; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: odurojr@wisc.edu., Spivey T; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Moore EM; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Meyerson H; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Yoest J; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Tomlinson B; Department of Hematology/Oncology, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Beck R; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Alouani D; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio., Sadri N; Department of Pathology and Laboratory Medicine, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: navid.sadri@uhhospitals.org.
Jazyk:	angličtina
Zdroj:	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2024 Sep; Vol. 37 (9), pp. 100534. Date of Electronic Publication: 2024 Jun 07.
DOI:	10.1016/j.modpat.2024.100534
Abstrakt:	The ability to detect low-level disease is key to our understanding of clonal heterogeneity in acute myeloid leukemia (AML) and residual disease that elude conventional assays and seed relapse. We developed a high-sensitivity next-generation sequencing (HS-NGS) clinical assay, able to reliably detect low levels (1 × 10 -5 ) of FLT3-ITD, a frequent, therapeutically targetable and prognostically relevant mutation in AML. By applying this assay to 289 longitudinal samples from 62 patients at initial diagnosis and/or clinical follow-up (mean follow-up of 22 months), we reveal the frequent occurrence of FLT3-ITD subclones at diagnosis and demonstrate a significantly decreased relapse risk when FLT3-ITD is cleared after induction or thereafter. We perform pairwise sequencing of diagnosis and relapse samples from 23 patients to uncover more detailed patterns of FLT3-ITD clonal evolution at relapse than is detectable by less-sensitive assays. Finally, we show that rising ITD level during consecutive biopsies is a harbinger of impending relapse. Our findings corroborate the emerging clinical utility of high-sensitivity FLT3-ITD testing and expands our understanding of clonal dynamics in FLT3-ITD-positive AML. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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