Work

Targeting osteoclasts for treatment of high-risk B-cell acute lymphoblastic leukemia

Year: 2025

Type: article

Abstract: B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Outcomes have improved significantly over the last 50 years, with 5-year overall survival approaching 90%, but certain subgroups have inferior prognoses, especially those with high-risk genetic alterations in their leukemia cells, such as BCR-ABL1 or relapsed disease [ 1 ]. The tumor microenvironment is known to play an integral role in the development and progression of cancer. For hematological malignancies, the bone marrow (BM) microenvironment serves as the site of initiation, progression, and relapse. It consists of different cell types, including hematopoietic stem and progenitor cells, immune cells, fibroblasts, endothelial cells, osteoblasts, and osteoclasts. Clinical studies in children diagnosed with ALL have demonstrated bone loss and changes in the BM microenvironment during disease development [ 2 , 3 ], suggesting that restoring the healthy BM microenvironment represents an attractive therapeutic avenue, especially for children with high-risk leukemia where dose-limiting toxicities of conventional chemotherapeutic agents have prevented further improvement.

Source: Blood Cancer Journal

DOI: 10.1038/s41408-025-01239-3