B-cell lymphoma discovery could lead to new treatments
A protein called CD19 can help drive a form of non-Hodgkin's lymphoma called B-cell lymphoma, rather than just being a 'marker' for the disease, according to US scientists.
The finding suggests that treatments in development, that home in on the protein and deliver drugs to cancer cells, might be more potent than suspected. And combining them with other targeted drugs in development could enhance this effect.
CD19 is found on the surface of immune cells called B-cells. It receives and passes on signals from the cell's exterior which switch on genes inside the cell's nucleus.
Since it is only found on B-cells, researchers have tried to exploit this to specifically target drugs to B-cell lymphomas, which make up about two out of five cases of non-Hodgkin's lymphoma.
In the new laboratory research, published in the Journal of Clinical Investigation, scientists at University of Pennsylvania in Philadelphia looked at the molecular changes that occurred when normal B-cells developed into lymphoma cells.
They found that CD19 maintained levels of a protein called MYC, which drives a range of cancers.
When the scientists blocked CD19, levels of MYC decreased, and the growth rate of the cancer cells also slowed.
The researchers also looked at tissue samples from patients with B-cell lymphoma. They found that patients with higher levels of CD19 also tended to have higher levels of MYC - confirming their laboratory observations. Crucially, they found that these patients had poorer survival rates.
Cancer Research UK's chief clinician, Professor Peter Johnson, said the research suggested that drug combinations aimed at targeting the CD19 pathway could be effective if trials confirm these results.
"CD19 has long been known to be a 'marker' for cancers that arise from B-cells, and drugs that use this molecule to target B-cell cancers are now entering clinical trials - including one funded by Cancer Research UK. But it hasn't been clear whether the protein was actively involved in the disease, or just a passive bystander.
"This fascinating new research shows that CD19 can switch on a complex molecular cascade inside B-cells that ultimately fuels the cancer's growth, and highlights the key molecules involved. It suggests that anti-CD19 drugs might work through a different mechanism than we thought. Interestingly, there are also drugs in trial that target the molecules 'downstream' of CD19, raising the possibility that combining them with anti-CD19 drugs could prove an effective strategy to treat patients with B-cell lymphomas."
"This will need confirming in the laboratory and in subsequent clinical trials," he cautioned.
Copyright Press Association 2012
- Chung et al. CD19 is a major B cell receptor–independent activator of MYC-driven B-lymphomagenesis. J Clin Invest (2012) DOI: 10.1172/JCI45851