High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) outcomes have improved, yet relapses remain a significant challenge.
• Bone morphogenetic protein 4 (BMP4) is explored as a potential prognostic biomarker and pathogenic factor in BCP-ALL.

Purpose of the Study:

• To investigate the prognostic relevance of BMP4 expression in pediatric BCP-ALL.
• To assess the pathogenic role of BMP4 in BCP-ALL development and central nervous system (CNS) involvement.

Main Methods:

• Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyzed BMP4 mRNA expression in leukemic blasts from 115 pediatric BCP-ALL patients.
• A validation cohort of 236 BCP-ALL patients was used.
• An NSG mouse xenograft model was employed to study BMP4's role in disease progression and CNS involvement.

Main Results:

• Elevated BMP4 mRNA levels (upper quartile) correlated with higher cumulative relapse incidence, worse 5-year event-free survival, and increased CNS involvement.
• These associations persisted even in patients with non-high risk of relapse.
• High BMP4 expression in a xenograft model promoted disease progression, CNS infiltration, chemoresistance, and angiogenesis.

Conclusions:

• BMP4 expression serves as a valuable biomarker for identifying pediatric BCP-ALL patients at higher risk of poor outcomes, including those in low-/intermediate-risk groups.
• Targeting BMP4 signaling presents a promising therapeutic strategy to combat leukemic CNS disease in BCP-ALL.