Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient. García-Álvarez, M., Yeguas, A., Jiménez, C., Medina-Herrera, A., González-Calle, V., Hernández-Ruano, M., Maldonado, R., Aires, I., Casquero, C., Sánchez-Villares, I., Balanzategui, A., Sarasquete, M. E., Alcoceba, M., Vidriales, M. B., González-Díaz, M., García-Sanz, R., & Chillón, M. C. Biomedicines, 12(1):66, December, 2023. Number: 1 Publisher: Multidisciplinary Digital Publishing Institute![Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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.
@article{garcia-alvarez_single-cell_2023,
title = {Single-{Cell} {DNA} {Sequencing} and {Immunophenotypic} {Profiling} to {Track} {Clonal} {Evolution} in an {Acute} {Myeloid} {Leukemia} {Patient}},
volume = {12},
copyright = {http://creativecommons.org/licenses/by/3.0/},
issn = {2227-9059},
url = {https://www.mdpi.com/2227-9059/12/1/66},
doi = {10.3390/biomedicines12010066},
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.},
language = {en},
number = {1},
urldate = {2024-01-24},
journal = {Biomedicines},
author = {García-Álvarez, María and Yeguas, Ana and Jiménez, Cristina and Medina-Herrera, Alejandro and González-Calle, Verónica and Hernández-Ruano, Montserrat and Maldonado, Rebeca and Aires, Irene and Casquero, Cristina and Sánchez-Villares, Inmaculada and Balanzategui, Ana and Sarasquete, María Eugenia and Alcoceba, Miguel and Vidriales, María Belén and González-Díaz, Marcos and García-Sanz, Ramón and Chillón, María Carmen},
month = dec,
year = {2023},
note = {Number: 1
Publisher: Multidisciplinary Digital Publishing Institute},
keywords = {Custom, Custom Pan-Myeloid Panel, Custom Panel, FLT3-ITD, acute myeloid leukemia, gilteritinib and clonal evolution, immunophenotype, midostaurin, next-generation sequencing, single-cell DNA sequencing},
pages = {66},
}
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