Among pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), BMP4 may be predictive of outcomes and may constitute a viable therapeutic target, according to research published in Blood.

The researchers noted that up to 15% of patients with low- or intermediate-risk BCP-ALL relapse, and this includes central nervous system (CNS) relapse. CNS involvement is implicated in approximately 60% of deaths in this patient population.

Although several cytokines, chemokines, and adhesion molecules are known to be involved in CNS involvement in the setting of leukemia, it was not previously known the extent to which BMP4 may play a role. For this study, researchers explored the role of BMP4 in CNS involvement and outcomes in pediatric BCP-ALL.


Continue Reading

Overall, samples taken from 115 patients at diagnosis were included in the retrospective part of this study. Analysis suggested that higher mRNA expression levels of BMP4 (defined as expression levels above the third quartile) were linked with both a higher risk of relapse (P =.0317) and worse event-free survival outcomes (P =.026). Similar findings were noted for CNS relapse risk (P =.036).

Analyses of a validation cohort of 236 patients appeared to support these findings. A mouse xenograft model suggested that blocking the canonical BMP signaling pathway may decrease CNS infiltration, potentially improving clinical outcomes. Analysis also suggested that BMP4 promotes chemoresistance and a proinflammatory tumor microenvironment.

“Taken together, clinical and experimental results shown in this study indicate an important role for BMP4 in BCP-ALL development and CNS leukemic infiltration and point out that BMP4 could be a new therapeutic target to prevent leukemic CNS involvement and disease relapse,” the authors wrote in their report.

Disclosures: The study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Fernández-Sevilla LM, Valencia J, Ortiz-Sánchez P, et al. High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes. Blood. 2022;139(22):3303-3313. doi:10.1182/blood.2021013506

This article originally appeared on Hematology Advisor