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

The in-frame internal tandem duplication (ITD) of the FMS-like tyrosine kinase 3 ( ) gene is an important negative prognostic marker in acute myeloid leukemia (AML). -ITD monitoring is essential for patients at relapse or those receiving -targeted therapies. Fragment analysis (FA) is commonly used t...

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Bibliographic Details
Published in:Cancers 2022-12, Vol.14 (24), p.6121
Main Authors: Lee, Jong-Mi, Park, Silvia, Hwang, Insik, Kang, Dain, Cho, Byung Sik, Kim, Hee-Je, Ahn, Ari, Kim, Myungshin, Kim, Yonggoo
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Algorithms
Bioinformatics
Chemotherapy
Flt3 protein
Hematopoietic stem cells
Kinases
Leukemia
Medical prognosis
Morphology
Next-generation sequencing
Patients
Protein-tyrosine kinase
Remission (Medicine)
Software
Stem cell transplantation
Survival analysis
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Summary:The in-frame internal tandem duplication (ITD) of the FMS-like tyrosine kinase 3 ( ) gene is an important negative prognostic marker in acute myeloid leukemia (AML). -ITD monitoring is essential for patients at relapse or those receiving -targeted therapies. Fragment analysis (FA) is commonly used to detect and quantify -ITDs; however, detecting low-burden -ITDs after a treatment is challenging. We, therefore, developed a customized, next-generation sequencing (NGS)-based -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 -ITD.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14246121