Bone Marrow Microbiome, Proteome Differences Between Patients With ET, Prefibrotic PMF

Changes in the bone marrow microbiome and proteome can help distinguish between patients with myeloproliferative neoplasms (MPN) and essential thrombocythemia (ET) and those with prefibrotic primary myelofibrosis (pre-PMF), according to a study presented at the 65th ASH Annual Meeting & Exposition, which is taking place December 9-12 in San Diego, California.

“It is increasingly recognized that the bone marrow microenvironment, including inflammation and metabolic imbalances, influences disease progression. So far, there have been few studies focusing on the combined analysis of the bone marrow microbiome and proteome in MPN patients,” the researchers wrote.

In this study, Anqi Zhang and colleagues assessed changes in the bone marrow microbiome and proteome and their association with pathogenesis in patients with ET and pre-PMF. They analyzed the formalin-fixed, paraffin-embedded (FFPE) bone marrow slides from 6 patients with untreated pre-PMF (median age, 64 years) and 7 patients with ET (median age, 53 years). They then conducted proteomic analysis of the FFPE tissue slides of bone marrow from 13 patients using 4-dimensional data-independent acquisition technology. The bone marrow microenvironment was analyzed using 2bRAD-M sequencing.

The results showed that JAK2 V617F mutations were more frequent in patients with pre-PMF than in those with ET (17.9% vs 55.8%; P=.001). The researchers observed that lactate dehydrogenase in patients with pre-PMF was higher than in those with ET, and this difference was statistically significant (P=.007). Also, the researchers found that high-density lipoprotein cholesterol in the pre-PMF patients was appreciably reduced, indicating a difference in lipid metabolism between patients with pre-PMF and those with ET.

Overall, the study uncovered that bone marrow microbial diversity and richness was higher in patients with pre-PMF. “We have shown that there are multilevel differences, including the proteome and microbiome, between ET and pre-PMF patients. This could potentially provide new insights for distinguishing and treating these 2 disease subtypes,” the investigators concluded.

Reference

Zhang A, Sun T, Yang R, Zhang L. Comparative analysis of bone marrow microbiome and proteome differences between essential thrombocythaemia and prefibrotic primary myelofibrosis. Abstract #4577. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.