Gene Mutation Suggests New Treatment Target for Specific Lymphoma

WEDNESDAY Dec. 22, 2010 -- Researchers have identified a gene mutation that may offer a target for new treatments for a type of lymphoma.

The team found that a mutation of the MYD88 gene is one of the most frequent genetic abnormalities in patients with this cancer, known as large B cell lymphoma.

The MYD88 gene encodes a protein that is crucial for normal immune response to invading microorganisms. The mutation identified in this study can cause uncontrolled cellular signaling, resulting in the survival of malignant cells.

A subgroup of the large B cell lymphoma that has a dismally low cure rate -- known as the activated B cell-like (ABC) subtype -- appears particularly susceptible to the gene.

Lymphoma is a cancer of the blood that starts in white blood cells. Diffuse large B cell lymphoma, in turn, is a type of non-Hodgkin lymphoma, in which white blood cells known as lymphocytes multiply out of control. There are three subtypes of diffuse large cell lymphoma: Patients with the ABC form have the lowest rate of three-year survival, with only 40 percent reaching that milestone.

The researchers, led by scientists at the U.S. National Cancer Institute (NCI), found that the mutant form of MYD88 allowed the ABC lymphoma cells to survive but the non-mutated version did not.

One more piece of the puzzle was unraveled through another cell-signalling protein called IRAK4. The researchers found it functioned as an enzyme to modify a substance called IRAK1, which was required for the mutant MYD88 protein to promote lymphoma cell survival.

"We believe the results of this study may provide a method to identify patients with the [ABC subtype] whose tumors may depend upon MYD88 signaling," study author Louis M. Staudt, of NCI's Center for Cancer Research, said in an NCI news release.

These patients, he said, may thus benefit from therapies targeting "regulatory pathways that sustain the survival of these lymphoma cells."

The study appears online Dec. 22 in the journal Nature.

More information

The American Cancer Society has more about non-Hodgkin lymphoma.

Posted: December 2010


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