The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution
© 2020, The Author(s). The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA seq...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1107828 http://hdl.handle.net/20.500.11937/81655 |
| _version_ | 1848764398891433984 |
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| author | Anderson, D. Skut, P. Hughes, Anastasia Ferrari, E. Tickner, J. Xu, J. Mullin, B.H. Tang, D. Malinge, S. Kees, U.R. Kotecha, Rishi Lassmann, T. Cheung, Laurence |
| author_facet | Anderson, D. Skut, P. Hughes, Anastasia Ferrari, E. Tickner, J. Xu, J. Mullin, B.H. Tang, D. Malinge, S. Kees, U.R. Kotecha, Rishi Lassmann, T. Cheung, Laurence |
| author_sort | Anderson, D. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2020, The Author(s). The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression. Normal pro- and pre-B cells were found to be the most affected at the earliest stages of disease and this was associated with changes in expression of genes regulated by the AP1-transcription factor complex and regulatory factors NELFE, MYC and BCL11A. Granulocyte–macrophage progenitors show reduced expression of the tumor suppressor long non-coding RNA Neat1 and disruptions in the rate of transcription. Intercellular communication networks revealed monocyte-dendritic precursors to be consistently active during B-ALL progression, with enriched processes including cytokine-mediated signaling pathway, neutrophil-mediated immunity and regulation of cell migration and proliferation. In addition, we confirmed that the hematopoietic stem and progenitor cell compartment was perturbed during leukemogenesis. These findings extend our understanding of the complexity of changes and molecular interactions among the normal cells of the BMM during B-ALL progression. |
| first_indexed | 2025-11-14T11:18:44Z |
| format | Journal Article |
| id | curtin-20.500.11937-81655 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:18:44Z |
| publishDate | 2020 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-816552020-11-20T06:58:22Z The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution Anderson, D. Skut, P. Hughes, Anastasia Ferrari, E. Tickner, J. Xu, J. Mullin, B.H. Tang, D. Malinge, S. Kees, U.R. Kotecha, Rishi Lassmann, T. Cheung, Laurence © 2020, The Author(s). The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression. Normal pro- and pre-B cells were found to be the most affected at the earliest stages of disease and this was associated with changes in expression of genes regulated by the AP1-transcription factor complex and regulatory factors NELFE, MYC and BCL11A. Granulocyte–macrophage progenitors show reduced expression of the tumor suppressor long non-coding RNA Neat1 and disruptions in the rate of transcription. Intercellular communication networks revealed monocyte-dendritic precursors to be consistently active during B-ALL progression, with enriched processes including cytokine-mediated signaling pathway, neutrophil-mediated immunity and regulation of cell migration and proliferation. In addition, we confirmed that the hematopoietic stem and progenitor cell compartment was perturbed during leukemogenesis. These findings extend our understanding of the complexity of changes and molecular interactions among the normal cells of the BMM during B-ALL progression. 2020 Journal Article http://hdl.handle.net/20.500.11937/81655 10.1038/s41598-020-76157-4 eng http://purl.org/au-research/grants/nhmrc/1107828 http://purl.org/au-research/grants/nhmrc/1127156 http://purl.org/au-research/grants/nhmrc/1163933 http://purl.org/au-research/grants/nhmrc/1142627 http://creativecommons.org/licenses/by/4.0/ fulltext |
| spellingShingle | Anderson, D. Skut, P. Hughes, Anastasia Ferrari, E. Tickner, J. Xu, J. Mullin, B.H. Tang, D. Malinge, S. Kees, U.R. Kotecha, Rishi Lassmann, T. Cheung, Laurence The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution |
| title | The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution |
| title_full | The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution |
| title_fullStr | The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution |
| title_full_unstemmed | The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution |
| title_short | The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution |
| title_sort | bone marrow microenvironment of pre-b acute lymphoblastic leukemia at single-cell resolution |
| url | http://purl.org/au-research/grants/nhmrc/1107828 http://purl.org/au-research/grants/nhmrc/1107828 http://purl.org/au-research/grants/nhmrc/1107828 http://purl.org/au-research/grants/nhmrc/1107828 http://hdl.handle.net/20.500.11937/81655 |