The identification of new molecular markers for multiple myeloma paves the way for more precise therapies

Researchers at Cima and Clinica Universidad de Navarra have identified new molecular mechanisms underlying multiple myeloma. This type of hematologic cancer, which affects the bone marrow, is characterized by its resistance to treatment, leading to relapses in patients. 

The study focused on analyzing which transcription factors (key proteins that regulate gene activation) are essential in the development of multiple myeloma. This research, conducted at the Cancer Center Clínica Universidad de Navarra, builds on previous work that studied the complete epigenome of myeloma. “In those 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,” explains Dr. Nahia Gómez-Echarte, a postdoctoral researcher at CIMA and first author of the study, whose results have just been published in the latest issue of the scientific journal Blood.

“We have also confirmed that its expression is a good biomarker, because it allows us to stratify patients based on better or worse prognoses,” notes Dr. Xabier Agirre, principal investigator of the Cima Epigenetics Group and co-director of the study, along with Drs. Felipe Prósper and Edurne San José-Enériz.

Predicting Response to Treatment

The study analyzed 230 transcription factors identified using computational tools. Subsequently, 54 factors that were indeed expressed in myeloma cells were selected. For each of these transcription factors, 10 different CRISPR guides were designed to determine whether inhibiting these factors was key to the viability of myeloma cells. This analysis identified 22 factors that are potentially essential for the development of this type of cancer.

Among these transcription factors, scientists at Cima have demonstrated that IRF2 plays key biological roles, such as regulating necroptosis (a type of cell death), migration, and cell cycle control in multiple myeloma. Furthermore, the study reveals that IRF2 expression levels allow for better stratification of patients, distinguishing those with a better or worse prognosis. As Dr. Agirre notes, “incorporating this biomarker into current multiple myeloma classification systems could improve the ability to predict patients’ response to treatments.”

The study, conducted within the framework of the CIBER Cancer (CIBERONC), received public funding from the Carlos III Health Institute and the Government of Navarre, as well as support from private institutions such as the Paula and Rodger Riney Foundation.

Bibliographic reference:
IRF2 is an Essential Transcription Factor with Pathogenic and Prognostic Impact in Multiple Myeloma. Blood. June 25, 2026;147(26):3195-3208.
doi: 10.1182/blood.2025029422.