Among pediatric patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL), bone morphogenetic protein 4 (BMP4) may be predictive of outcomes, and may constitute a viable therapeutic target, according to research published in Blood.

BCP-ALL is the most frequently diagnosed pediatric cancer. Although new treatments have yielded improved clinical outcomes over the past several decades, up to 15% of patients with low- or intermediate-risk disease relapse, including central nervous system (CNS) relapse. CNS involvement is, furthermore, 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.

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 also 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.

BMP4 Expression Levels May Predict Clinical Outcomes in Pediatric BCP-ALL

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