In this case report, we present a very rare instance of a pediatric B-cell ALL (B-ALL) patient with a SPINK1 NM 003122: c.194 + 2T>C heterozygous variant (rs148954387) and AAP, highlighting the intricate interplay between genetic predisposition and asparaginase therapy in AAP development. This evidence concerns the gene SPINK1 and acute lymphoblastic leukemia.