Researchers from Spain identified a set of molecular markers that can help identify patients with systemic mastocytosis (SM) who are at a higher risk of disease progression and poor survival. This can ensure that doctors follow these patients more closely and initiate cytoreductive treatment early.

SM is typically driven by the KIT D816V mutation. However, other genes have also been found to be involved in the malignant transformation of SM. Twelve genes have been recurrently reported to be mutated in patients with the disease, including ASXL1, CBL, DNMT3A, EZH2, JAK2, KRAS, NRAS, SF3B1, RUNX1, SF3B1, SRSF2, and TET2.

Some of these mutations affect transcription factors and signaling pathways, while others are in genes that play a role in epigenetic regulatory mechanisms or alternative messenger RNA splicing.

Read more about the different types of SM

This finding can help explain the clinical heterogeneity of SM even though most patients have the KIT D816V transformation, regardless of whether their disease is advanced.

“Just as nowadays the measurement of allele burden of the KIT D816V mutation has become an important predictor of treatment response assessment and survival,” the authors wrote.

“Further analysis of the [variant allele frequency] for these later genes might provide a more reliable marker for assessing tumor burden as compared to other clinical and/or laboratory parameters, which can be also altered by medication or intercurrent processes.”

SM is a clonal hematopoietic stem cell disease characterized by expanding and accumulating neoplastic mast cells in different organs and tissues such as the bone marrow, liver, spleen, and gastrointestinal tract. The disease is classified as indolent, smoldering, with an associated hematologic neoplasm, aggressive, or mast cell leukemia.

The study is published in Cancers.


González-López O, Muñoz-González JI, Orfao A, Álvarez-Twose I, García-Montero AC. Comprehensive analysis of acquired genetic variants and their prognostic impact in systemic mastocytosis. Cancers (Basel). 2022;14(10):2487. doi:10.3390/cancers14102487