New research published in Hematology suggests that serum chitotriosidase enzyme (CHIT1) could serve as a biomarker for polycythemia vera (PV), a Philadelphia-chromosome negative myeloproliferative neoplasm.

Macrophages, granulocytes and epithelial cells produce CHIT1, which defends mammals against infection from chitin-containing insects, fungi and bacteria, and also plays a role in mediating immune responses and regulating tissue remodeling.

DNA strand and test tubes. Source: Getty

Elevated CHIT1 levels indicate macrophage activation and expansion in a number of diseases, including Gaucher’s disease, beta-thalassemia, sarcoidosis, Wegener’s granulomatosis and some kinds of malaria. CHIT1 might also promote inflammation-related tissue remodeling and fibrosis, as overexpression occurs in hepatic fibrosis and cirrhosis, chronic obstructive pulmonary disease, atherosclerosis and interstitial lung disease.

As the myeloproliferative neoplasms (MPNs) polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis are characterized by overproduction of macrophage-producing cells, inflammation and fibrosis, the researchers sought to determine whether CHIT1 levels correlated with development or progression of MPNs.

They measured CHIT1 in 28 patients with PV, 27 with ET, 17 with PMF, 19 with post-PV or post-ET (secondary) myelofibrosis and 25 healthy controls with similar age and sex distribution between July 2014 and February 2017.

All patients included in the study had bone marrow biopsies for clinical reasons unrelated to the study and had blood samples taken within six months of the date of bone marrow biopsy.

They found significantly elevated levels of CHIT1 in patients with PV and post-PV myelofibrosis compared to healthy controls, but not in patients with ET and post-ET myelofibrosis or primary myelofibrosis.

In patients with PV, higher levels of CHIT1 correlated with increased hemoglobin, hematocrit and absolute basophil count. Hematocrit and hemoglobin levels are distinct PV characteristics and considered “major” diagnostic criteria in the World Health Organization classification of MPNs.

CHIT1 also indicated the presence of reticulin fibrosis in bone marrow in PV patients. Similar correlations were not detected in patients with ET or primary or secondary myelofibrosis.

The authors noted that macrophages regulate the pathological erythropoiesis in PV and contribute to the creation of the “erythroid” phenotype. The authors said that “elevated CHIT1 in PV patients and a positive correlation between CHIT1 and these PV-defining features, hemoglobin, hematocrit and absolute basophil count, might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin.”

The authors noted that targeting the CHIT1 activation cascade diminished inflammation and fibrosis in studies on animals and could provide a targeted therapy option for PV, though the risk of fungal and protozoal infections would need to be considered.

The authors concluded that “CHIT1 could be considered as a circulating biomarker in PV,” an observation that “highlights the role of the tumor microenvironment in pathogenesis and the clinical presentation of MPNs, which might help in recognizing new therapeutic targets in these neoplasms.”