Study shows protein marker helps predict aggressive myeloma

A study linked high expression of the protein desmoglein-2 (DSG2) to lower survival in people with myeloma.

Data suggest that high DSG2 expression is associated with worse survival even after accounting for well-established genetic risk factors of aggressive disease. The researchers proposed that adding DSG2 analysis to existing genetic analyses may help provide more accurate prognoses for myeloma patients.

“Rapidly identifying patients who are likely to have more aggressive forms of the disease is critical because it can influence treatment decisions from the very beginning,” Barbara McClure, PhD, co-author of the study and a research associate at Adelaide University in Australia, said in a university news story. “DSG2 has the potential to become an additional tool that helps clinicians better predict how a patient’s disease will behave and tailor treatment accordingly.”

The study, “Elevated desmoglein-2 expression in multiple myeloma is a prognostic marker across genomic subtypes with impact on high-risk cytogenetics and a distinct gene expression profile,” was published as a letter to the editor in the British Journal of Haematology.

Myeloma is a form of blood cancer caused by the uncontrolled growth of plasma cells, a type of immune cell, in the bone marrow. Previous work has established that myeloma containing certain specific genetic mutations tends to be more aggressive, leading to worse outcomes for patients, so these genetic markers are routinely tested to help guide care.

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Probing a key protein

Myeloma cells express the DSG2 protein at high levels in roughly one-third of people with the disease. This protein plays roles in cell growth and survival, key processes that enable cancers to progress and spread. Prior research has linked high DSG2 levels to an increased risk of mortality in myeloma patients, but it remains unclear whether DSG2 provides any additional prognostic information beyond the well-established genetic markers.

To learn more, scientists analyzed data from more than 600 people newly diagnosed with myeloma who were followed as part of a clinical trial (NCT01454297) that ran from 2011 to 2023 and tracked how underlying molecular profiles affected long-term outcomes. That trial was funded by the Multiple Myeloma Research Foundation.

Statistical analyses showed that high DSG2 expression was associated with a significantly increased risk of death, even after accounting for other factors like age and treatments used. High DSG2 was linked with worse outcomes in patients both with and without genetic risk factors, indicating that the protein marker provides information beyond these well-established markers. This “suggests that DSG2 expression analysis would complement the current risk stratification strategies, aiding in the rapid identification of high-risk patients at diagnosis,” the researchers said.

“While genomic testing has improved our ability to identify high-risk disease, some patients who appear to have standard-risk myeloma still experience rapid progression and poor survival,” said study co-author Claudine Bonder, a research professor at Adelaide. “Our findings show that high DSG2 levels can identify patients with a particularly aggressive type of multiple myeloma that may not be captured by existing risk-stratification approaches.”

The scientists highlighted the need for further work to better understand how DSG2 may affect the underlying biology of myeloma cells. More research is warranted to determine whether DSG2 might be a useful treatment target, they said.

“If we can better understand the role DSG2 plays in disease progression, it may open the door to new precision medicine approaches to improve outcomes for myeloma patients with high-risk disease,” McClure said.