A rare genetic change in a teenager with systemic mastocytosis (SM) and acute myeloid leukemia (AML) showed that broader testing is needed to correctly diagnose and treat unusual cases, and it may directly affect patient outcomes when standard tests miss key mutations.
Doctors recently described in the Journal of Pediatric Hematology/Oncology a 17-year-old girl who came in with two months of fatigue, weakness, intermittent fever, gum bleeding and widespread petechiae (red-brown spots caused by bleeding under the skin).
Blood tests showed severe anemia with hemoglobin of 6.2 g/dL, a leukocyte count of 6.98 × 10⁹/L and platelets of 17 × 10⁹/L. A blood smear revealed 5% blasts, while bone marrow testing showed 45% blasts with Auer rods, along with an unusual increase in mast cells.
What is a mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body.?
Mast cells are specialized cells of the immune system that mediate inflammatory responses and allergic reactions. They are found in the body’s connective tissue.
Further testing confirmed a leukemia subtype driven by a RUNX1::RUNX1T1 fusion, a mutation caused by DNA from chromosomes 8 and 21 combining. However, routine genetic testing via next-generation sequencing did not find additional mutations.
Because the bone marrow findings suggested mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults., doctors used a different genetic testing method, polymerase chain reaction, which identified a rare KIT exon 8 deletion called p.Asp419del. Her serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM., a marker linked to mast cell diseaseMast cell disease A group of conditions in which mast cells behave abnormally by building up in excess, releasing chemicals too easily or both. Includes mastocytosis, mast cell activation syndrome and hereditary alpha-tryptasemia., was markedly elevated at 174 μg/L.
Read more about SM testing and diagnosis
“Our patient had the KIT-activating p.Asp419del mutation in the exon 8 of the KIT gene, which is found in < 3% of adult SM but is seen in 15% to 20% cases of childhood cutaneous mastocytosis,” the patient’s doctors explained.
The patient met diagnostic criteria for SM based on abnormal mast cell shape, CD25 expression and the KIT mutation.
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She received intensive chemotherapy with daunorubicin and cytarabine followed by additional treatment and imatinib. Her leukemia went into remission, but clusters of mast cells continued to appear in repeated bone marrow tests, showing that the SM persisted.
Plans were made for a stem cell transplant, but her condition worsened with severe infection and febrile neutropenia (fever in someone with a low white blood cell count). She died from refractory septic shock during consolidation therapy. Notably, she never developed the skin findings often seen in SM, which made the condition harder to recognize earlier.
For patients, this case highlights that rare mutations can be missed with standard testing, which may delay diagnosis or limit treatment choices. It also shows that even when leukemia improves, mast cell disease may continue and require separate management.
