May 10, 2023
Vicki Morre, PhD
A study involving patients with myeloproliferative neoplasms (MPNs) revealed high frequencies of myeloid-derived suppressor cells (MDSCs) in bone marrow. The study findings were reported in the journal Advances in Molecular Pathology.
In their report, the study investigators explained that while MDSCs have been shown to be more frequent in the peripheral blood of patients with MPNs, the frequency of these in the bone marrow had not been well understood.
In this study, they evaluated the frequencies of MDSCs in the peripheral blood and bone marrow of patients with MPNs and correlated these levels with other clinical and laboratory parameters.
Overall, 64 patients with MPNs were included in the study. For bone marrow analyses, the study recruited 17 patients with essential thrombocythemia (ET), 29 patients with polycythemia vera (PV), and 18 patients with primary myelofibrosis (PMF), in addition to 5 healthy donors. Analyses of peripheral blood included 11 patients with ET, 11 patients with PV, 9 patients with PMF, and 11 donors without hematologic malignancies.
Included patients had been previously untreated, and multiple clinical and laboratory parameters, including JAK2 and CALR variant status, were obtained from them at the time of diagnosis. MDSCs were evaluated through flow cytometry, and other assays were also performed.
Median ages were 56 years for patients with ET, 60 years for patients with PV, and 62 years for patients with PMF. Assays showed that in the bone marrow percentages of total MDSCs (T-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) were significantly greater across patients with MPNs than in healthy donors.
These differences were greatest for patients with PMF, who had a mean T-MDSC level of 55.37%, compared with healthy donors, who had a mean T-MDSC level of 25.36% (P =.004). The mean PMN-MDSC level was 54.58% for patients with PMF, compared with 18.8% for healthy donors (P =.008), as well.
Peripheral blood analyses also showed significant elevations in T-MDSC and PMN-MDSC levels in patients with MPNs, compared with healthy donors, apart from a trend of moderately higher percentage of circulating T-MDSCs in patients with ET that did not reach significance.
There were, however, not correlations seen between elevated MDSCs in the bone marrow and parameters of age, hepatomegaly, leukocytes, hemoglobin, or platelet levels. JAK2 or CALR status also appeared uncorrelated with MDSC levels.
The study investigators reported an additional finding of an apparent immunosuppressive function of MDSCs from patients with MPNs. In patient samples that had undergone MDSC depletion, T-cell proliferation rates were significantly higher than they were without MDSC depletion, across MPN types.
“In summary, this study demonstrated increased frequency levels of MDSCs in the bone marrow of MPNs patients,” the investigators wrote in their report. Although MDSC levels did not show correlations with multiple clinical parameters or with mutations of JAK2 or CALR genes, the investigators pointed out myelofibrosis intensity appeared associated with MDSC frequency in bone marrow.
Reference
Kapor S, Momčilovič S, Kapor S, et al. Increase in frequency of myeloid-derived suppressor cells in the bone marrow of myeloproliferative neoplasm: potential implications in myelofibrosis. Adv Exp Med Biol. 2023;1408:273-290. doi:10.1007/978-3-031-26163-3_15