The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia

Alicia Garcia-Gimenez; Simon E Richardson

doi:10.3389/fonc.2023.1150612

The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia

Front Oncol. 2023 Mar 7:13:1150612. doi: 10.3389/fonc.2023.1150612. eCollection 2023.

Authors

Alicia Garcia-Gimenez¹, Simon E Richardson^{1

2}

Affiliations

¹ Department of Haematology, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
² Cambridge University Hospitals, Cambridge, United Kingdom.

Abstract

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignant disorder of immature B lineage immune progenitors and is the commonest cancer in children. Despite treatment advances it remains a leading cause of death in childhood and response rates in adults remain poor. A preleukemic state predisposing children to BCP-ALL frequently arises in utero, with an incidence far higher than that of transformed leukemia, offering the potential for early intervention to prevent disease. Understanding the natural history of this disease requires an appreciation of how cell-extrinsic pressures, including microenvironment, immune surveillance and chemotherapy direct cell-intrinsic genetic and epigenetic evolution. In this review, we outline how microenvironmental factors interact with BCP-ALL at different stages of tumorigenesis and highlight emerging therapeutic avenues.

Keywords: B- cell precursor acute lymphoblastic leukemia (BCP-ALL); chemoresistance; epigenetics; microenvironment; tumor evolution.

Publication types

Review

Grants and funding

SR is supported by a Clinician Scientist Fellowship from Cancer. Research UK (C67279/A27957) and Leukaemia UK John Goldman. Fellowship (2022/JGF/004). Research in the Wellcome - MRC. Cambridge Stem Cell Institute is funded by a grant from the Wellcome Trust (203151/Z/16/Z). Research in the Cancer Research. UK Cambridge Centre is supported by a Cancer Research UK Major CentreAward (C9685/A25117).