Редкая мутация KIT привела к ошибочной диагностике острого лейкоза у подростка

A first-reported case of systemic mastocytosis with associated acute myeloid leukemia (SM-AML) harboring a KIT exon 8 p.Asp419del mutation demonstrates that comprehensive molecular testing is essential for accurate diagnosis and may influence therapeutic decision-making in atypical presentations. Routine next-generation sequencing (NGS) failed to identify the mutation, underscoring a critical diagnostic gap, according to the case study published in the Journal of Pediatric Hematology/ Oncology. The case highlights the diagnostic challenge posed by occult mastocytosis, which may be obscured by blast burden, reinforcing the need for heightened clinical suspicion and expanded molecular assessment when standard testing is unrevealing. A 17-year-old female presented with a 2-month history of fatigue, weakness, intermittent fever, gum bleeding, and petechiae, requiring multiple transfusions. Laboratory evaluation revealed hemoglobin of 6.2 g/dL, leukocyte count of 6.98 × 109/L, and platelet count of 17 × 109/L. Peripheral smear showed 5% blasts with dysgranulopoiesis, while bone marrow examination demonstrated 45% blasts with Auer rods and prominent interstitial mast cells, some with atypical hypogranular morphology. Immunophenotyping identified aberrant CD25 expression on mast cells without CD2 or CD30 positivity. NGS detected a RUNX1::RUNX1T1 fusion at a read count of 115,430.96 per million but did not reveal additional somatic mutations despite sequencing depth exceeding 1000×. Given morphologic suspicion, targeted polymerase chain reaction identified a KIT exon 8 deletion (c.1255_1257delGAC; p.Asp419del), and serum tryptase was markedly elevated at 174 μg/L. The patient met International Consensus Classification minor criteria for SM, including atypical mast cell morphology, CD25 expression, and an activating KIT mutation, with concurrent fulfillment of World Health Organization 2022 criteria for SM. Induction chemotherapy with daunorubicin and cytarabine was followed by reinduction with imatinib, which achieved remission of the AML; however, mast cell aggregates persisted across serial bone marrow evaluations. Despite plans for hematopoietic stem cell transplantation, the clinical course was complicated by febrile neutropenia and refractory septic shock, resulting in death during consolidation therapy. Notably, there were no cutaneous manifestations of mastocytosis throughout the disease course, further complicating recognition. KIT mutations occur in approximately 20% to 40% of RUNX1::RUNX1T1-positive AML, most commonly involving exon 17 at codon p.D816V. In contrast, exon 8 alterations are rare in this setting. Functional studies of p.Asp419del suggest ligand-independent KIT activation with partial sensitivity to imatinib, supporting its role as a gain-of-function mutation. “This case highlights the diagnostic and therapeutic challenges of SM-AML, particularly when associated with noncanonical KIT mutations,” stated the authors. “The rare KIT exon 8 deletion (p.Asp419del), previously unreported in SM-AML, emphasizes the need for comprehensive molecular testing, including high-sensitivity PCR, when clinical and morphologic suspicion for SM exists.” This article originally appeared on Rare Disease Advisor References: Balraam V, Nayak AR, Dass J, et al. Unresponsive systemic mastocytosis in a young AML with RUNX1::RUNX1T1 fusion with rare KIT c.1255_1257delGAC mutation: a clinical deadlock. J Pediatr Hematol Oncol. Published online June 26, 2026. doi:10.1097/MPH.0000000000003232