Author:
Anderson Denise,Skut Patrycja,Hughes Anastasia M.,Ferrari Emanuela,Tickner Jennifer,Xu Jiake,Mullin Benjamin H.,Tang Dave,Malinge Sébastien,Kees Ursula R.,Kotecha Rishi S.,Lassmann Timo,Cheung Laurence C.
Abstract
Abstract
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.
Funder
Cancer Research Trust Western Australia
Children’s Leukaemia and Cancer Research Foundation
Cancer Council Western Australia
Government of Western Australia
Curtin University
Edith Cowan University
The University of Western Australia
Telethon Kids Institute
National Health and Medical Research Council of Australia
Feilman Foundation
Publisher
Springer Science and Business Media LLC
Cited by
22 articles.
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