Prognostic significance of caspase 8 associated protein 2 (CASP8AP2) in childhood b cell acute lymphoblastic Leukemia

Improved treatment of childhood acute lymphoblastic leukemia (ALL) depends on the identification of new molecular markers that can predict treatment response and clinical outcome. Examination of the expression patterns of a set of genes at the RNA level is one of these new modalities. The prognostic significance of caspase-8-associated protein 2 (CASP8AP2), an apoptosis-related gene, in pediatric ALL is controversial.

A prospective study of 70 newly diagnosed ALL patients who were treated in the National Cancer Institute (NCI), Cairo University during the period from 1st of October 2019 till the end of September 2023, to measure the CASP8AP2 expression level in bone marrow samples at the time of diagnosis and at the end of induction therapy using real-time quantitative PCR, and to assess its relation with different prevalent prognostic variables and disease outcome. All cases were followed up till end of December 2024.

Higher initial CASP8AP2 gene expression was associated with hyperdiploid karyotyping (p = 0.009), molecularly favorable mutations (p = 0.002), early induction response (p = 0.025), and low-risk patients (p < 0.001) and had a significant impact on lowering events in the first 3 years of follow-up (p = 0.001). Meanwhile, examining post-induction gene levels failed to show similar results.

Higher initial CASP8AP2 gene expression was associated with favorable impact on event-free survival in pediatric ALL patients. Post-induction levels did not show similar correlation. Future larger studies are needed to confirm the favorable association and to search for other possibly related prognostic factors to further refine risk stratification.