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dc.contributor.authorAnderson, D.
dc.contributor.authorSkut, P.
dc.contributor.authorHughes, Anastasia
dc.contributor.authorFerrari, E.
dc.contributor.authorTickner, J.
dc.contributor.authorXu, J.
dc.contributor.authorMullin, B.H.
dc.contributor.authorTang, D.
dc.contributor.authorMalinge, S.
dc.contributor.authorKees, U.R.
dc.contributor.authorKotecha, Rishi
dc.contributor.authorLassmann, T.
dc.contributor.authorCheung, Laurence
dc.identifier.citationAnderson, D. and Skut, P. and Hughes, A.M. and Ferrari, E. and Tickner, J. and Xu, J. and Mullin, B.H. et al. 2020. The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution. Scientific Reports. 10 (1): Article No. 19173.

© 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.

dc.titleThe bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution
dc.typeJournal Article
dcterms.source.titleScientific Reports
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusOpen access
curtin.facultyFaculty of Health Sciences
curtin.contributor.orcidCheung, Laurence [0000-0001-6298-5288]
curtin.contributor.orcidKotecha, Rishi [0000-0003-1836-4075]
curtin.contributor.scopusauthoridCheung, Laurence [56663936300]

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