Philadelphia chromosome‐like B‐acute lymphoblastic leukemia and disseminated juvenile xanthogranulomatosis with shared KRAS mutation.

This article reports the first known case of a pediatric patient with Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like B-ALL) complicated by disseminated juvenile xanthogranuloma (JXG), both sharing a KRAS G12D mutation. The patient, a 12-year-old male, developed refractory leukemia alongside histiocytic proliferation and hemophagocytic lymphohistiocytosis (HLH), and was treated with a mitogen-activated protein kinase kinase (MEK) inhibitor, trametinib, targeting the shared mutation. This targeted therapy led to clinical improvement and remission, allowing subsequent hematopoietic cell transplantation, although the patient ultimately died from transplant-related complications. The case highlights a potential clonal relationship between histiocytic disorders and Ph-like B-ALL and suggests that RAS-MAPK pathway mutations may be therapeutically actionable in such complex presentations.