Unresponsive Systemic Mastocytosis in a Young AML With RUNX1::RUNX1T1 Fusion With Rare KIT c.1255_1257delGAC Mutation: A Clinical Deadlock

BACKGROUND: Systemic mastocytosis (SM) with associated acute myeloid leukemia (AML) is a rare malignancy usually linked to KIT p.D816V mutations. OBSERVATIONS: We report a 17-year-old female with RUNX1::RUNX1T1-positive AML and florid mast cell proliferation harboring a rare KIT exon 8 deletion (p.Asp419del). Diagnosis required integration of morphology, immunophenotyping, and polymerase chain reaction, as routine NGS failed to detect the mutation. Despite remission following intensive chemotherapy and imatinib, the patient developed persistent mastocytosis and succumbed to septic shock. CONCLUSIONS: This first reported case of SM-AML with KIT p.Asp419del highlights the need for comprehensive molecular testing and tailored therapy in atypical presentations.