Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient
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Published:2023-12-27
Issue:1
Volume:12
Page:66
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ISSN:2227-9059
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Container-title:Biomedicines
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language:en
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Short-container-title:Biomedicines
Author:
García-Álvarez María1, Yeguas Ana2, Jiménez Cristina1ORCID, Medina-Herrera Alejandro1, González-Calle Verónica1, Hernández-Ruano Montserrat1, Maldonado Rebeca1, Aires Irene1, Casquero Cristina1, Sánchez-Villares Inmaculada1, Balanzategui Ana1, Sarasquete María Eugenia1, Alcoceba Miguel1ORCID, Vidriales María Belén1, González-Díaz Marcos1, García-Sanz Ramón1ORCID, Chillón María Carmen1ORCID
Affiliation:
1. Hematology Department, University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC), 37007 Salamanca, Spain 2. Hematology Department, Complejo Asistencial Universitario de Palencia, 34005 Palencia, Spain
Abstract
Single-cell DNA sequencing can address the sequence of somatic genetic events during myeloid transformation in relapsed acute myeloid leukemia (AML). We present an NPM1-mutated AML patient with an initial low ratio of FLT3-ITD (low-risk ELN-2017), treated with midostaurin combined with standard chemotherapy as front-line treatment, and with salvage therapy plus gilteritinib following allogenic stem cell transplantation after relapse. Simultaneous single-cell DNA sequencing and cell-surface immunophenotyping was used in diagnostic and relapse samples to understand the clinical scenario of this patient and to reconstruct the clonal composition of both tumors. Four independent clones were present before treatment: DNMT3A/DNMT3A/NPM1 (63.9%), DNMT3A/DNMT3A (13.9%), DNMT3A/DNMT3A/NPM1/FLT3 (13.8%), as well as a wild-type clone (8.3%), but only the minor clone with FLT3-ITD survived and expanded after therapy, being the most represented one (58.6%) at relapse. FLT3-ITD was subclonal and was found only in the myeloid blast population (CD38/CD117/CD123). Our study shows the usefulness of this approach to reveal the clonal architecture of the leukemia and the identification of small subclones at diagnosis and relapse that may explain how the neoplastic cells can escape from the activity of different treatments in a stepwise process that impedes the disease cure despite different stages of complete remission.
Funder
INSTITUTO DE SALUD CARLOS III Accelerator Award Program Spanish Society of Hematology Foundation
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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