Unique Giant Cancer Cells Found in Patients With Myelodysplastic Syndromes

Researchers found Polypoid Giant Cancer Cells (PGCC) in the peripheral blood of 46% of patients with myelodysplastic syndromes (MDS), suggesting they may play a role in hematological malignancies.

Findings were published in Medical Oncology.

MDS are a group of stem cell disorders that can transform into secondary acute myeloid leukemia (AML). The disorders are also characterized by dysplastic hematopoietic cells and cytopenias in the blood. Apart from the less than 10% of individuals who can be treated with allogeneic transplantation, MDS are incurable.

“Since most therapies fail to prevent rapid clonal evolution and disease resistance, new and noninvasive predictive markers are needed to monitor patients and adapt the therapeutic strategy,” the researchers explained.

To address this knowledge gap, they used ISET (Isolation by SizE of Tumor cells, Rarecells Diagnostics), a very sensitive approach to isolate cells larger than mature leukocytes, to look for cellular markers in patients with MDS and controls. They addressed 158 peripheral blood samples from 99 patients and 76 samples from 66 healthy individuals.

By enriching large cells, they discovered a relevant number of giant cells with 1 or multiple nuclei.

Specifically, data showed “a total of 680 Giant Cells, defined as cells having a size of 40 microns or larger in 46 MDS patients (80 samples) and 28 Giant Cells in 11 healthy individuals (11 samples).”PGCC are heterogenous cells that range in size from 25 to 300 µm.

Researchers then studied the Giant Cells using immunolabeling with megakaryocytes and tumor-specific markers, which revealed these cells in patients with MDS primarily express tumor markers. Previous studies have shown PGCC may initiate tumorigenesis and tumor recurrence after therapy in solid cancers.

“According to reported studies, increase in cell size may serve as a response to environmental stresses switching proliferative mitosis to intranuclear replication,” the authors explained.

In addition, a high rate of cells similar to PGCC—dysplastic hypogranular megakaryocytes—have been found in more than 80% of bone marrow samples from patients with MDS. However, the Giant Cells described in the current analysis express tumor markers telomerase, syncytin, and Runx2, and macrophage markers that are not expressed by cells of the megakaryocyte series, the authors said.

Most cells identified were also positive for the CD61 marker, and nearly 70% with a size of at least 40 µm were positive to a cocktail of macrophage markers (CD11b, CD68 CD163).

When the researchers conducted a longitudinal analysis of samples, they found patients and healthy controls who did not have any Giant Cells in initial collection did not show them in another collection after a 200-week follow-up. Those who did show the cells on initial collection consistently showed them on subsequent ones, and some showed an increase in Giant Cells over time.

Results of the current study require more investigation, the authors noted.

“Further in vitro studies are needed to explore [the cells’] proliferative capacity, their resistance to treatment, and their possible ability to generate blasts cells by budding.” Animal studies could be performed to evaluate Giant Cells’ tumorigenic/leukemic potential, while in patients, researchers could assess their presence and phenotype in bone marrow.

However, results could aid in efforts to better understand the potential clinical impact of these Giant Cells in patients with liquid cancers, they concluded.

“Ultimately, our findings provide more questions than answers but open a new field of investigations aimed at understanding if the [Giant Cells] we detected in MDS patients can be considered the equivalent of PGCC described in solid cancers.”

Reference:

Ali AM, BenMohamed F, Decina A, et al. Circulating cancer giant cells with unique characteristics frequently found in patients with myelodysplastic syndromes (MDS). Med Oncol. Published online June 14, 2023. doi:10.1007/s12032-023-02064-z