Expression of SETD2, a protein responsible for maintaining the integrity of the genetic information, may predict the overall survival of patients with systemic mastocytosis (SM) as well as differentiate indolent SM from other forms of SM.

The data were presented during the European Hematology Association (EHA) Hybrid Congress 2023, held in Frankfurt, Germany, this June.

To evaluate the clinical and prognostic significance of SETD2 levels, the researchers collected clinical and follow-up information from 88 patients with SM and analyzed their bone marrow samples at the time of diagnosis.

They analyzed the presence of skin lesions, severe anaphylaxis reactions, osteoporosis or osteopenia, palpable splenomegaly, and other organomegalies, as well as the blood count alterations, serum alkaline phosphatase, lactate dehydrogenase, and serum tryptase levels.

According to the results, diverse SETD2 values were found in different World Health Organization disease subtypes. The median SETD2 values were 0 in aggressive SM (range, 0.0-0.80), 0 in mast cell leukemia (range, 0.00-0.76), 0 in SM with an associated hematological neoplasm (range, 0.00-1.00), 0.24 in smoldering SM (range, 0.0-0.86), and 0.69 in indolent SM (range, 0.00-1.00).

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Moreover, a SETD2 expression value of 0.425 could tell apart indolent SM from other SM subtypes with a sensitivity of 84.09% and specificity of 86.36%. Seven of 44 (15.9%) patients with indolent SM had a SETD2 value lower than 0.425, compared with 34 of 37 (91.9%) patients with advanced SM.

Based on the same SETD2 expression value, patients were divided into 2 groups that had significantly different overall survival rates. Those with a SETD2 expression value lower than 0.425 and those with SETD2 expression value of at least 0.425 had significant variations in age, presence of skin lesions, severe anaphylaxis reactions, palpable splenomegaly, hemoglobin and platelets level, alkaline phosphatase, and serum tryptase.

“In the subset of the non-advanced SM forms, attempts have been made in several large series to integrate clinical and genetic information to fine-tune a risk model capable of identifying cases at risk of progression. Recently, non-genomic loss of function of the SETD2 histone methyltransferase has been reported in SM, and it has been proposed that it may cooperate and potentiate the effects of KIT in advSM,” Rondoni and colleagues explained.


Rondoni M, Mancini M, Papayannidis C, et al. SETD2 protein levels are a novel predictor of overall survival in systemic mastocytosis. Presented at: European Hematological Association (EHA) 2023 annual congress, Vienna, Austria, June 9-11, 2023.