Protein marker may help predict myeloma outcomes
IRF2 also may offer a target for future treatment strategies
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A protein called IRF2 may help drive myeloma, and measuring its levels could help predict outcomes among people with the blood cancer, a new study reports.
Researchers also believe this protein may be a useful therapeutic target for new myeloma treatment strategies.
“IRF2 represents a new prognostic biomarker and a promising therapeutic target for the development of innovative therapeutic strategies for patients with [myeloma],” researchers wrote in the study, “IRF2 is an essential transcription factor with pathogenic and prognostic impact in multiple myeloma,” which was published in Blood.
Protein may help drive myeloma
Myeloma is a form of blood cancer that arises due to the uncontrolled growth of certain plasma cells, a type of immune cell, in the bone marrow. The molecular mechanisms that control myeloma cell growth are not fully understood, but data suggest that abnormal activity of a class of proteins called transcription factors may play a role.
Transcription factors are proteins that bind specific sequences in a cell’s DNA, where they act as on-off switches, turning certain genes on or off. In doing so, transcription factors play key roles in controlling what a cell does and how it behaves.
In this study, scientists paired computational analyses with laboratory experiments, aiming to identify transcription factors that contribute to the abnormal growth of myeloma cells. These tests identified several transcription factors previously linked to myeloma, but they also zeroed in on IRF2, uncovering an essential, previously unknown role for this transcription factor in myeloma biology.
Earlier work suggested that transcription factors may play a role in epigenomic changes in myeloma — changes that affect how genes are turned on or off. “In [previous] studies, we discovered that transcription factors could play a key role in the epigenomic alterations of multiple myeloma. In the study we have just published, we demonstrate the role of IRF2, a transcription factor whose role in this disease was previously unknown and which may become a promising therapeutic target,” Nahia Gómez-Echarte, PhD, first author of the study at Cima and Clinica Universidad de Navarra in Spain, said in a university news story.
Higher IRF2 levels linked to worse outcomes
The researchers’ experiments indicated that IRF2 regulates genes and biological pathways involved in myeloma cell survival, growth, and migration — features that can help cancers develop and progress. IRF2 also appeared to help myeloma cells avoid necroptosis, a form of programmed cell death.
“IRF2 plays an essential role as a repressor or activator of critical pathways associated with the [disease mechanisms] of [multiple myeloma],” the researchers wrote.
The researchers then examined IRF2 expression levels in a dataset of 619 people with myeloma and found that those with higher IRF2 expression had shorter progression-free survival — meaning less time before the cancer worsened — and shorter overall survival.
“We have … confirmed that [IRF2’s] expression is a good biomarker, because it allows us to stratify patients based on better or worse prognoses,” said Xabier Agirre, PhD, study coauthor at Cima and Clinica Universidad de Navarra.
The scientists noted that further work is needed to validate IRF2 as a prognostic biomarker and explore its potential as a therapeutic target. “Although more … studies should be conducted to fully define the clinical potential of IRF2, this study establishes a critical foundation and paves the way for the development of innovative inhibitors targeting IRF2,” they wrote.
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