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Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution
Pediatric acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts, and it is divided into the AMKL patients with Down syndrome (DS-AMKL) and AMKL patients without DS (non-DS-AMKL). Pediatric non-DS-AMKL is a heterogeneous disease...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394455/ https://www.ncbi.nlm.nih.gov/pubmed/36003795 http://dx.doi.org/10.3389/fonc.2022.915833 |
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author | Su, Narun Li, Zifeng Yang, Jiapeng Fu, Yang Zhu, Xiaohua Miao, Hui Yu, Yi Jiang, Wenjin Le, Jun Qian, Xiaowen Wang, Hongsheng Qian, Maoxiang Zhai, Xiaowen |
author_facet | Su, Narun Li, Zifeng Yang, Jiapeng Fu, Yang Zhu, Xiaohua Miao, Hui Yu, Yi Jiang, Wenjin Le, Jun Qian, Xiaowen Wang, Hongsheng Qian, Maoxiang Zhai, Xiaowen |
author_sort | Su, Narun |
collection | PubMed |
description | Pediatric acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts, and it is divided into the AMKL patients with Down syndrome (DS-AMKL) and AMKL patients without DS (non-DS-AMKL). Pediatric non-DS-AMKL is a heterogeneous disease with extremely poor outcome. We performed single-cell RNA sequencing (scRNA-seq) of the bone marrow from two CBFA2T3-GLIS2 fusion-positive and one RBM15-MKL1 fusion-positive non-DS-AMKL children. Meanwhile, we downloaded the scRNA-seq data of normal megakaryocyte (MK) cells of the fetal liver and bone marrow from healthy donors as normal controls. We conducted cell clustering, cell-type identification, inferCNV analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Monocle2 analysis to investigate the intratumoral heterogeneity of AMKL. Using canonical markers, we identified and characterized the abnormal blasts and other normal immune cells from three AMKL samples. We found intratumoral heterogeneity of AMKL in various cell-type proportions, malignant cells’ diverse copy number variations (CNVs), maturities, significant genes expressions, and enriched pathways. We also identified potential markers for pediatric AMKL, namely, RACK1, ELOB, TRIR, NOP53, SELENOH, and CD81. Our work offered insight into the heterogeneity of pediatric acute megakaryoblastic leukemia and established the single-cell transcriptomic landscape of AMKL for the first time. |
format | Online Article Text |
id | pubmed-9394455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93944552022-08-23 Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution Su, Narun Li, Zifeng Yang, Jiapeng Fu, Yang Zhu, Xiaohua Miao, Hui Yu, Yi Jiang, Wenjin Le, Jun Qian, Xiaowen Wang, Hongsheng Qian, Maoxiang Zhai, Xiaowen Front Oncol Oncology Pediatric acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts, and it is divided into the AMKL patients with Down syndrome (DS-AMKL) and AMKL patients without DS (non-DS-AMKL). Pediatric non-DS-AMKL is a heterogeneous disease with extremely poor outcome. We performed single-cell RNA sequencing (scRNA-seq) of the bone marrow from two CBFA2T3-GLIS2 fusion-positive and one RBM15-MKL1 fusion-positive non-DS-AMKL children. Meanwhile, we downloaded the scRNA-seq data of normal megakaryocyte (MK) cells of the fetal liver and bone marrow from healthy donors as normal controls. We conducted cell clustering, cell-type identification, inferCNV analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Monocle2 analysis to investigate the intratumoral heterogeneity of AMKL. Using canonical markers, we identified and characterized the abnormal blasts and other normal immune cells from three AMKL samples. We found intratumoral heterogeneity of AMKL in various cell-type proportions, malignant cells’ diverse copy number variations (CNVs), maturities, significant genes expressions, and enriched pathways. We also identified potential markers for pediatric AMKL, namely, RACK1, ELOB, TRIR, NOP53, SELENOH, and CD81. Our work offered insight into the heterogeneity of pediatric acute megakaryoblastic leukemia and established the single-cell transcriptomic landscape of AMKL for the first time. Frontiers Media S.A. 2022-08-08 /pmc/articles/PMC9394455/ /pubmed/36003795 http://dx.doi.org/10.3389/fonc.2022.915833 Text en Copyright © 2022 Su, Li, Yang, Fu, Zhu, Miao, Yu, Jiang, Le, Qian, Wang, Qian and Zhai https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Su, Narun Li, Zifeng Yang, Jiapeng Fu, Yang Zhu, Xiaohua Miao, Hui Yu, Yi Jiang, Wenjin Le, Jun Qian, Xiaowen Wang, Hongsheng Qian, Maoxiang Zhai, Xiaowen Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution |
title | Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution |
title_full | Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution |
title_fullStr | Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution |
title_full_unstemmed | Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution |
title_short | Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution |
title_sort | revealing the intratumoral heterogeneity of non-ds acute megakaryoblastic leukemia in single-cell resolution |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394455/ https://www.ncbi.nlm.nih.gov/pubmed/36003795 http://dx.doi.org/10.3389/fonc.2022.915833 |
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