Waldenstrom macroglobulinemia (WM) is incredibly difficult to treat. In addition to having no cures, the condition only has one approved treatment option. However, researchers now believe that combining drugs, specifically BET inhibitors, could provide a new, effective, and more accessible option for patients with WM. Read the full study findings published in Epigenomics.
Waldenstrom Macroglobulinemia (WM)
Doctors are not sure of the exact cause of Waldenstrom macroglobulinemia (WM), a rare lymphoma that begins in lymphocytes, or blood cells that play a role in the immune system. However, an estimated 90% of patients have MYD88 gene mutations, suggesting a potential genetic cause. WM begins in B lymphocytes, which later begin created an abnormal version of immunoglobulin M (IgM) called macroglobulin. As the cancer cells multiply, they cause hyperviscosity, or thickened blood. Typically, WM affects Caucasians more than other ethnic groups. This rare blood cancer is also 2x more likely to occur in males than in females, and the risk increases as people age.
In many cases, patients with WM will not have any symptoms, especially in early stages of cancer. However, as the cancer progresses, symptoms may include:
- Fatigue
- Anemia (low red blood cell counts)
- Shortness of breath
- Muscle weakness
- Frequent infections
- Unintended weight loss
- Diarrhea
- Easy bruising and bleeding
- Nosebleeds
- Blurry vision
- Dizziness and low concentration
- Headaches
- Swollen lymph nodes
- Numb hands and feet
BET Inhibitors
During their research, researchers from the University of New Hampshire wanted to understand the epigenetics of Waldenstrom macroglobulinemia, with a particular focus on the epigenetics of these cancerous cells. The CDC describes epigenetics as:
the study of how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence.
Examples of epigenetic changes include histone modification, DNA methylation, and non-coding RNA. In this specific research, the research team looked at bromodomain and extraterminal (BET), proteins that act as epigenetic readers. The focus on BET centered around prior research which has linked BET to a number of conditions. Thus, BET inhibitors could potentially stop the growth and progression of cancer cells through regulating and blocking gene expression.
To test this theory, researchers treated WM cells with JQ-1 and I-BET-762, both of which are BET inhibitors. Although neither drug caused the death of cancerous cells, JQ-1 helped reduce cancerous cell spread by 70%. Next, researchers evaluated whether BET inhibitors would be more potent in conjunction with other therapies, such as Ibrutinib (the current approved treatment), venetoclax, or panabinostat. Ultimately, they determined that BET inhibitors, alongside panabinostat, was the most effective treatment for WM.
Read the source article here.
