Concepts in B cell acute lymphoblastic leukemia pathogenesis

Abstract

B cell acute lymphoblastic leukemia (B-ALL) arises from genetic alterations impacting B cell progenitors, ultimately leading to clinically overt disease. Extensive collaborative efforts in basic and clinical research have significantly improved patient prognoses. Nevertheless, a subset of patients demonstrate resistance to conventional chemotherapeutic approaches and emerging immunotherapeutic interventions. This review highlights the mechanistic underpinnings governing B-ALL transformation. Beginning with exploring normative B cell lymphopoiesis, we delineate the influence of recurrent germline and somatic genetic aberrations on the perturbation of B cell progenitor differentiation and protumorigenic signaling, thereby facilitating the neoplastic transformation underlying B-ALL progression. Additionally, we highlight recent advances in the multifaceted landscape of B-ALL, encompassing metabolic reprogramming, microbiome influences, inflammation, and the discernible impact of socioeconomic and racial disparities on B-ALL transformation and patient survival.

Keywords: B cell acute lymphoblastic leukemia; disparities; leukemic transformation; patient survival; tumor metabolism.

Fig. 1.

Multifaceted interactions impacting B-ALL transformation and survival. Schematic provides an overview of the diverse mechanisms contributing to B-ALL transformation. These mechanisms include B cell differentiation blocks, aberrant oncogenic signaling, metabolic reprogramming, microbiome influence, inflammatory processes, and the impact of socioeconomic and racial disparities. Together, these factors influence both the initiation and sustained survival of B-ALL cells. Figure created with BioRender.com.