Potential value of high-throughput single-cell DNA sequencing of Juvenile myelomonocytic leukemia: report of two cases.

Autor: Volchkov EV; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia. volchcov.egor@yandex.ru.; Laboratory of Single Cell Biology, Research Institute of Molecular and Cellular Medicine, RUDN University, Moscow, 117198, Russia. volchcov.egor@yandex.ru., Khozyainova AA; Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634009, Russia., Gurzhikhanova MK; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Larionova IV; Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634009, Russia., Matveev VE; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Evseev DA; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Ignatova AK; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Menyailo ME; Laboratory of Single Cell Biology, Research Institute of Molecular and Cellular Medicine, RUDN University, Moscow, 117198, Russia.; Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634009, Russia., Venyov DA; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Vorobev RS; Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634009, Russia., Semchenkova AA; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Olshanskaya YV; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia., Denisov EV; Laboratory of Single Cell Biology, Research Institute of Molecular and Cellular Medicine, RUDN University, Moscow, 117198, Russia.; Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634009, Russia., Maschan MA; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI) of Ministry of Healthсare of the Russian Federation, 1, Samory Mashela St., Moscow, 117997, Russia. mmaschan@yandex.ru.
Jazyk: angličtina
Zdroj: NPJ systems biology and applications [NPJ Syst Biol Appl] 2023 Sep 09; Vol. 9 (1), pp. 41. Date of Electronic Publication: 2023 Sep 09.
DOI: 10.1038/s41540-023-00303-7
Abstrakt: Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of early childhood that develops due to mutations in the genes of the RAS-signaling pathway. Next-generation high throughput sequencing (NGS) enables identification of various secondary molecular genetic events that can facilitate JMML progression and transformation into secondary acute myeloid leukemia (sAML). The methods of single-cell DNA sequencing (scDNA-seq) enable overcoming limitations of bulk NGS and exploring genetic heterogeneity at the level of individual cells, which can help in a better understanding of the mechanisms leading to JMML progression and provide an opportunity to evaluate the response of leukemia to therapy. In the present work, we applied a two-step droplet microfluidics approach to detect DNA alterations among thousands of single cells and to analyze clonal dynamics in two JMML patients with sAML transformation before and after hematopoietic stem cell transplantation (HSCT). At the time of diagnosis both of our patients harbored only "canonical" mutations in the RAS signaling pathway genes detected by targeted DNA sequencing. Analysis of samples from the time of transformation JMML to sAML revealed additional genetic events that are potential drivers for disease progression in both patients. ScDNA-seq was able to measure of chimerism level and detect a residual tumor clone in the second patient after HSCT (sensitivity of less than 0.1% tumor cells). The data obtained demonstrate the value of scDNA-seq to assess the clonal evolution of JMML to sAML, response to therapy and engraftment monitoring.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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