Should we be doing more research in multiple myeloma on certain ethniticies like the Hispanic or Black populations to drive more personalized therapy? A new finding for Hispanic myeloma patients demonstrates why this is important.
It was recently discovered that Hispanic myeloma patients are more likely to have a mutation in a protein called IRF4, a master regulator that activates cancer mutations. Interferon Regulatory Factor 4, or IRF4, is a protein that controls the expression of the correct genes in the correct cells. This is critical to regulate immune system responses, immune cell developent, cell growth regulation and metabolism. It is also essential as plasma cells mature into variouos types of immune system cells. It also regulates over 100 genes that are quiet in plasma cells. (Agnaraelli et al., n.d., 52-58)
It has also emerged as a protein that activates genetic mutations or translocations. The translocation 6(6;14)(p25;q32) affected by the IRF4 mutation is found in about 21% of myeloma cases. Other mutations can be associated with IRF4 and myeloma patients with low IRF4 can have longer survival rates.
The Next Generation Sequencing (NGS) test can identify this mutation, however NGS tests are still typically only performed in academic research (Chiringova et al., n.d., 2-9).
In a recent clinical trial (Peres et al., 2022), the IRF4 mutation was found to be most common in Hispanic patients and non-existent in Black patients. Having the IRF4 mutation is linked with worse outcomes and overall survival.
Finding these new, more personalized targets are important for new drug development as myeloma remains an incurable disease.
Importantly, lenalidomide (Revlimid) decreases the amount of IRF4 which dexamethasone increases it (Lopez-Girona et al., 2011). Remember that lower IRF4 is better, so understanding these nuances in myeloma could affect how "standard" myeloma drugs are prescribed to patients based on their genetics.
Myeloma cells become "addicted" to IRF4 and a family of regulator genes called MYC. MYC is key in upsetting normal genetics and the normal lifecycle of cells. Both IRF4 and MYC regulate one another in myeloma cells, creating a positive loop for myeloma cell growth.
If MYC were targeted with a new myeloma drug, it could actually lead to a lowering of IRF4 as a result. (Chen & Gooding, 2022).
IRF4 is an important protein for gene expression and plays a significant role in the development of multiple myeloma. It is common and can lead to worse outcomes for patients. Studying these specific targets is important to identify the best possible personalized care, leading to better survival and higher quality of life. Ethnic differences do exist in myeloma and knowing more about how they are unique could help an entire sub-population of myeloma patients.
about the author
Andrea Robles is an International Medical Graduate, part of Healthtree’s patient navigator staff. She is committed to patient’s global wellness and finding a cure through research. She’s also a wife and mom of 3.