Histamine and serotonin levels in bone marrow obtained from patients during routine hematologic diagnostic procedures have been used as potential biomarkers of systemic mastocytosis (SM) and myeloproliferative disorders, according to the results of a study published in Stem Cell Reviews and Reports.

SM is characterized by an increased proliferation of mast cells—one of the main cells responsible for the production of histamine. In patients with SM, the excessive accumulation of mast cells is observed in a variety of organs, including the bone marrow.

Recognizing that the biosynthesis of histamine occurs mainly in mast cells and basophils, whereas the activity of serotonin takes place largely in the nervous system, the researchers sought to evaluate differences in histamine and serotonin concentrations in bone marrow, as well as to determine the suitability of histamine and serotonin as potential diagnostic biomarkers.

They theorized that histamine and serotonin levels measured in the bone marrow niche—the site where the storage cells for both of these compounds are produced—may be linked with either the cause of clinical abnormalities or an effect of the underlying pathogenic process.

An analytical method that used liquid chromatography and tandem mass spectrometry was developed and validated for determining histamine and serotonin concentrations simultaneously. Bone marrow niche material was obtained from patients hospitalized at the Department of Hematology, Oncology and Radiotherapy of the University of Zielona Góra, Multi-Specialist Provincial Hospital in Gorzów Wielkopolski, Poland. A total of 100 bone marrow samples were obtained from the patients.

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Results of the study showed that concentrations measured in all of the samples were 344.11±959.09 ng/mL for histamine and 0.61±3.69 ng/mL for serotonin. Overall, histamine levels in 67% of the samples were within the normal range of 20 to 200 ng/mL (ie, the normal blood levels), and 83% of all serotonin measurements and 97% of nonmalignant hematologic diseases were below the detection limit of 0.2 ng/mL.

According to statistical analyses, histamine levels were significantly higher in samples obtained from individuals with SM and myeloproliferative neoplasms than in samples obtained from patients with myelodysplastic syndromes, lymphoproliferative neoplasms, acute leukemias, or other nonmalignant hematologic diseases. No significant differences were observed, however, for serotonin levels between individual disease groups.

The authors concluded that, for the first time, their findings demonstrated that “the concentration of histamine in bone marrow is comparable to the values measured in blood in a physiological state” and noted “high levels of histamine in patients with myeloproliferative diseases.”

“Serotonin, on the other hand, is not produced in significant amounts by bone marrow, and its increased levels may indicate an increased proliferation of megakaryocytes in bone marrow,” they wrote.


Janus GT, Korbal U, Żukowski M, et al. Histamine and serotonin levels in bone marrow stem cells niche as potential biomarkers of systemic mastocytosis and myeloproliferative disorders. Stem Cell Rev Rep. Published online December 29, 2022. doi:10.1007/s12015-022-10502-0