FLT3-ITD Measurable Residual Disease Monitoring in Acute Myeloid Leukemia Using Next-Generation Sequencing

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Abstract

The in-frame internal tandem duplication (ITD) of the FMS-like tyrosine kinase 3 (FLT3) gene is an important negative prognostic marker in acute myeloid leukemia (AML). FLT3-ITD monitoring is essential for patients at relapse or those receiving FLT3-targeted therapies. Fragment analysis (FA) is commonly used to detect and quantify FLT3-ITDs; however, detecting low-burden FLT3-ITDs after a treatment is challenging. We, therefore, developed a customized, next-generation sequencing (NGS)-based FLT3-ITD assay that includes a new ITD-tracing algorithm, “SEED”, optimized for measurable residual disease (MRD) monitoring. NGS-SEED showed an enhanced sensitivity (0.001%) and has a superior performance over conventional fragment analysis. We further investigated the prognostic impact of MRD analyzed by NGS-SEED in AML patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). Our assay showed that the MRD assessed before and after HSCT were significantly associated with a risk of relapse and a poor overall survival, respectively, in a time-dependent analysis. Thus, this report highlighted the prognostic value of serial MRD monitoring using a sensitive method in a clinical setting of AML patients with FLT3-ITD.

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Lee, J. M., Park, S., Hwang, I., Kang, D., Cho, B. S., Kim, H. J., … Kim, Y. (2022). FLT3-ITD Measurable Residual Disease Monitoring in Acute Myeloid Leukemia Using Next-Generation Sequencing. Cancers, 14(24). https://doi.org/10.3390/cancers14246121

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