Characterization of mesenchymal stem cells in pre-B acute lymphoblastic leukemia

Anastasia M Hughes; Vincent Kuek; Joyce Oommen; Grace-Alyssa Chua; Maria van Loenhout; Sebastien Malinge; Rishi S Kotecha; Laurence C Cheung

doi:10.3389/fcell.2023.1005494

Characterization of mesenchymal stem cells in pre-B acute lymphoblastic leukemia

Front Cell Dev Biol. 2023 Jan 20:11:1005494. doi: 10.3389/fcell.2023.1005494. eCollection 2023.

Authors

Anastasia M Hughes^{1

2}, Vincent Kuek^{1

2

3}, Joyce Oommen¹, Grace-Alyssa Chua¹, Maria van Loenhout¹, Sebastien Malinge^{1

3}, Rishi S Kotecha^{1

2

3

4}, Laurence C Cheung^{1

2

5}

Affiliations

¹ Leukaemia Translational Research Laboratory, Telethon Kids Cancer Centre, Telethon Kids Institute, Perth, WA, Australia.
² Curtin Medical School, Curtin University, Perth, WA, Australia.
³ School of Medicine, University of Western Australia, Perth, WA, Australia.
⁴ Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation, Perth Children's Hospital, Perth, WA, Australia.
⁵ Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.

Abstract

Components of the bone marrow microenvironment (BMM) have been shown to mediate the way in which leukemia develops, progresses and responds to treatment. Increasing evidence shows that leukemic cells hijack the BMM, altering its functioning and establishing leukemia-supportive interactions with stromal and immune cells. While previous work has highlighted functional defects in the mesenchymal stem cell (MSC) population from the BMM of acute leukemias, thorough characterization and molecular profiling of MSCs in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, has not been conducted. Here, we investigated the cellular and transcriptome profiles of MSCs isolated from the BMM of an immunocompetent BCR-ABL1⁺ model of B-ALL. Leukemia-associated MSCs exhibited reduced self-renewal capacity in vitro and significant changes in numerous molecular signatures, including upregulation of inflammatory signaling pathways. Additionally, we found downregulation of genes involved in extracellular matrix organization and osteoblastogenesis in leukemia-associated MSCs. This study provides cellular and molecular insights into the role of MSCs during B-ALL progression.

Keywords: bone marrow; bone marrow microenvironment; leukemia; mesenchymal stem cell; pre-B cell acute lymphoblastic leukemia.

Grants and funding

This work was supported by the Child Cancer Research Foundation (CCRF) Perth, Western Australia, and by grant 1184963 awarded through the 2019 Priority-driven Collaborative Cancer Research Scheme, and co-funded by Cancer Australia, Cure Cancer and the Leukaemia Foundation of Australia. SM is supported by a Fellowship from the Cancer Council Western Australia. RSK is supported by a Fellowship from the National Health and Medical Research Council of Australia (NHMRC APP1142627). AMH is supported by a PhD Support Scholarship from the Tour de Cure (RSP-312–19/20) and an Australian Government Research Training Program (RTP) Scholarship.