FLT3-ITD Expression as a Potential Biomarker for the Assessment of Treatment Response in Patients with Acute Myeloid Leukemia

FLT3-internal tandem duplication (ITD) analysis is not typically performed in cDNA samples and is not considered an appropriate marker for monitoring measurable residual disease (MRD). The aims of this study were to compare FLT3-ITD mutation analysis in DNA and cDNA samples at diagnosis and to demon...

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Published in:Cancers 2022-08, Vol.14 (16), p.4006
Main Authors: Carbonell, Diego, Chicano, María, Cardero, Alfonso J., Gómez-Centurión, Ignacio, Bailén, Rebeca, Oarbeascoa, Gillen, Martínez-Señarís, Diana, Franco, Carolina, Muñiz, Paula, Anguita, Javier, Kwon, Mi, Díez-Martín, José Luis, Buño, Ismael, Martínez-Laperche, Carolina
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Biomarkers
Capillary electrophoresis
Cloning
Deoxyribonucleic acid
Diagnosis
DNA
Hematopoietic stem cells
Kinases
Leukemia
Medical prognosis
Mutation
Patients
Remission (Medicine)
Stem cell transplantation
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Summary:FLT3-internal tandem duplication (ITD) analysis is not typically performed in cDNA samples and is not considered an appropriate marker for monitoring measurable residual disease (MRD). The aims of this study were to compare FLT3-ITD mutation analysis in DNA and cDNA samples at diagnosis and to demonstrate the usefulness of its expression measurement as an MRD marker after allogeneic stem cell transplantation (allo-HSCT) or FLT3 inhibitor (FLT3i) administration. A total of 46 DNA and cDNA diagnosis samples, 102 DNA and cDNA post-allo-HSCT samples from 34 patients and 37 cDNA samples from 7 patients with refractory/relapse AML treated with FLT3i were assessed for the FLT3-ITD mutation through fragment analysis. In terms of sensitivity, the analysis of cDNA was superior to that of DNA, quantifying higher allelic ratio values in most cases at diagnosis, and thus optimizing the detection of minor clones and prognostic classification. Regarding the last sample before post-HSCT relapse, cDNA analysis anticipated relapse in most cases, unlike DNA analyses. With regard to the post-FLT3i follow-up, FLT3-ITD expression was reduced after the first FLT3i cycle when the treatment was effective, whereas it was not reduced in refractory patients. FLT3-ITD expression could be a useful additional biomarker at diagnosis and for the assessment of MRD after allo-HSCT and FLT3i in AML.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14164006