Study Finds Higher Risks for Some Women with DLBCL

A new study published in Cancer Discovery found higher risks for some women with diffuse large B-cell lymphoma (DLBCL). Researchers also found a possible treatment target that may help future therapies. 

Some women with DLBCL had higher risks

DLBCL is the most common type of non-Hodgkin lymphoma. Some types of DLBCL have different gene changes. These changes can affect how lymphoma grows and responds to treatment.

Researchers studied nearly 5,000 people from 14 studies. They looked at two genes called SPEN and NOTCH2. 

Women with changes in both genes had more than four times higher mortality risk than men with the same changes. 

The study focused on a subtype called BN2-DLBCL. Researchers had not seen this survival difference before in this subtype. 

The X chromosome may explain the difference

Women have two X chromosomes. Men have one. Usually, one X chromosome in women stays mostly inactive. The SPEN gene helps control this process. But damage to SPEN and NOTCH2 may turn some genes back on. 

One of these genes is called TLR7. TLR7 helps control immune signals in the body. Too much TLR7 activity may help lymphoma cells grow and survive. 

Researchers also found that this effect was not caused by female hormones. The same pattern appeared in animal studies after the ovaries were removed.

This finding may help explain why some women with this subtype have more aggressive lymphoma. 

Researchers found a possible treatment target

Researchers studied medicines called IRAK (interleukin-1 receptor-associated kinase) inhibitors. These treatments block signals linked to the TLR7 pathway. 

IRAK inhibitors are already being tested in clinical trials for other conditions.

In lab studies, IRAK inhibitors worked better against female lymphoma cells. Researchers also tested the treatment in animals. Tumor growth slowed during treatment.

Combining IRAK inhibitors with chemotherapy improved treatment effects further.

These treatments are not yet approved for DLBCL. More clinical trials are still needed. But the findings may help researchers develop more personalized treatments in the future. 

Researchers may need to rethink how this subtype develops

Earlier research suggested that this subtype of DLBCL started deep inside immune system response centers. 

But this study suggests the lymphoma may come from older immune cells. These cells are linked to aging, infections, and autoimmune conditions. 

This may help explain why some older adults develop this subtype of DLBCL.

Summary

This study found higher risks for some women with DLBCL linked to certain gene changes. Researchers also identified a possible treatment target that may help guide future DLBCL therapies. 

Sources: 

• SPEN loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and therapeutic vulnerabilities
• Study Finds DLBCL Subtype May Have Higher Mortality Risk in Female Patients