Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) appears to be associated with a worse prognosis than isolated SM and has a specific molecular pattern, according to a recently published study in ProQuest.
SM is characterized by the accumulation of abnormal mast cells in various tissues, which in turn can cause varied symptoms. In some rare cases, SM occurs alongside a non–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. myeloid neoplasm; this subtype is termed SM-AHN. Due to the rarity of SM-AHN, the demographic, clinical and molecular features of this combined condition remain poorly understood. The authors aimed to compare molecular features of patients with SM-AHN and patients with isolated SM.
What are the types of SM?
There are five subtypes of SM: indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases., the most common and least severe subtype; smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form., which can progress to more serious illness; aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases.; SM with an associated hematologic neoplasm; and mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis., the rarest and most severe subtype.
The study reviewed data from January 2020 through December 2024, identifying seven patients with SM-AHN and eight patients with isolated SM. Researchers gathered data regarding differences in age at presentation, blood parameters, mutational profiles and clinical outcomes. All patients were followed until the end of 2024 or until their death.
The analysis revealed that patients with SM-AHN were older at diagnosis compared to those with isolated SM. Additionally, the SM-AHN group presented with worse hematologic findings, including more frequent anemia (low hemoglobin), thrombocytopenia (low platelets) and circulating blasts (immature white cells). These findings suggest a more aggressive disease course in SM-AHN.
Read more about SM prognosis
Molecular profiling showed a markedly higher mutational burden in SM-AHN. While mutations in the KIT gene, especially the D816V variant, were common in both groups, the SM-AHN cases frequently contained additional mutations. The coexistence of these mutations points toward a more complex molecular origin which is different from that of isolated SM.
Although the small sample is an important limitation, the findings strongly suggest that SM-AHN should be regarded as a distinct disease with a more adverse prognosis than isolated SM.
“This combined disorder is associated with older age, worse hematologic parameters, a higher mutational burden, and poorer prognosis. The frequent co-occurrence of mutations in other genes, in addition to KIT mutations, highlights the complex molecular landscape,” the authors concluded.
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