Currently Viewing:
Newsroom
Currently Reading
Suspension of a Rural Syringe Service Program Increased Risks of HIV and HCV Acquisition
May 23, 2019 – Wallace Stephens
LifeScan Finds Partner to Move Into CGM Market
May 23, 2019 – Mary Caffrey
Lenalidomide Beats Standard of Care in Smoldering MM
May 23, 2019 – Samantha DiGrande
What We're Reading: Addressing Maternal Care Disparities; Eggs and Stroke Risk; CBD for Opioid Addiction
May 23, 2019 – AJMC Staff
High-Deductible Insurance Plans Create Barriers to COPD Care
May 22, 2019 – Wallace Stephens
Patients With Ovarian Cancer Could Benefit From More Genetic Testing
May 22, 2019 – Laura Joszt
What We're Reading: Vermont AG Sues Sackler Family; Half-Price Insulin; Asthma Rates Fall in LA
May 22, 2019 – AJMC Staff
Increasing Use of Primary Care May Lower Rates of Respiratory Failure
May 22, 2019 – Wallace Stephens
African American COPD Patients Underutilize Pulmonary Rehabilitation
May 21, 2019 – Wallace Stephens

Finding the Trigger That Sets Off Growth of Hodgkin Lymphoma Cells

Mary Caffrey
Cure rates for Hodgkin lymphoma are high, but survivors may live for decades with side effects from chemotherapy. Finding a new treatment target could lead to fewer toxic effects.
Recovery rates for Hodgkin lymphoma are relatively high—more than 90% of those with localized cancer are cured, as are 80% with advanced disease. But this good news is offset by the long-term effects of chemotherapy, which can lead to heart and lung problems, infertility, or secondary cancers.

Since many patients with Hodgkin lymphoma are older teens or young adults, the effects of chemotherapy last for decades. Thus, there is interest in finding less toxic ways to treat this disease, which accounts for about 8100 new cases a year, according to the American Cancer Society.

“We therefore need to develop new therapeutic approaches to help prevent such problems,” Claus Scheidereit, head of the research group on Signal Transduction in Tumor Cells at the Max Delbruck Center (MDC), said in a statement.

Scheidereit’s group worked with others at MDC and Charite University of Medicine in Berlin, led by Stephan Mathas, DMed, resulting in a paper in Blood that identifies a potential target for new therapies. Their discovery starts with something the research community has known for a while: the protein complex NF-κB, which controls DNA transcription and cell survival, exists in the nuclei of Hodgkin cells and plays a critical role in this cancer.

But what sets NF-κB in motion?

Normally, the transcription factor NF-κB lives in a cell’s cytoplasm and only temporarily migrates to the nucleus to control gene expression; something happens in Hodgkin lymphoma to cause NF-κB to stay in the nucleus and cause lymphoma cells to grow unchecked, releasing signals that draw white blood cells into the lymph nodes.

The paper in Blood focuses on a series of tests to determine which molecules produced by Hodgkin cells activated NF-κB. Through this process, “We identified one single factor that is secreted by Hodgkin’s cells and activates NF-κB; a signaling molecule called lymphotoxin-alpha, or LTA for short,” said Eva Kaergel, a research assistant and co-author of the study.

Tissue sample analyses confirmed that lymph nodes from Hodgkin patients produce high levels of LTA, and other tests shows that inhibiting LTA blocked NF-κB activity in the Hodgkin cells.

The Scheidereit team not only showed the importance of LTA in triggering NF-κB, they also showed how it set off the signals that elevated white blood cells in the lymphatic system and set the stage for cancer to spread. Separately, the experiments suggest that LTA can be turned on and turned off, which offers promise for alternatives to chemotherapy.

“Our work suggests that LTA could be a good target for diversifying the existing treatment strategies for Hodgkin’s lymphoma,” Scheidereit said.

Reference

von Hoff L, Kargel E, Franke V, et al. Autocrine LTA signaling drives NF-κB and JAK-STAT activity and myeloid gene expression in Hodgkin lymphoma. Blood. 2019;133:1489-1494. doi: 10.1182/blood-2018-08-871293.

Related Articles

Over the Past 2 Decades, Use of G-CSF in Non-Hodgkin Lymphoma Increased Significantly
Dr Alison Moskowitz Discusses When to Use Brentuximab Vedotin in Hodgkin Lymphoma
Chemo, Then Radiotherapy, May Boost Survival for Patients With Advanced Hodgkin Lymphoma
 
Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up