Common Gene Mutation Found in Hairy Cell Leukemia - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Common Gene Mutation Found in Hairy Cell Leukemia

A gene mutation that occurs in melanoma and other cancers has now been detected in hairy cell leukemia (HCL), a rare cancer of the blood. The mutation, called V600E, occurs in the BRAF gene and appears to contribute to the disease, researchers reported in the June 16 New England Journal of Medicine.

All 48 patients with HCL in the study had the mutation. Patients with HCL produce large numbers of abnormal B lymphocytes, a type of white blood cell. These abnormal cells appear “hairy” under a microscope and give the disease its name.

Dr. Enrico Tiacci of the University of Perugia, Italy, and his colleagues began by sequencing the complete exome (that is, all protein-coding regions of the genome) of both tumor and normal cells of a patient with HCL. This revealed five variants that were found specifically in tumor cells but not in normal cells, one of which was the V600E mutation in BRAF.

Little is known about the other four affected genes, but BRAF is often mutated in cancer, and the V600E mutation occurs frequently. The researchers then found this mutation in 47 other patients with HCL; it was, however, absent from 195 additional patients with other B-cell lymphomas or leukemias who were tested.
The presence of this mutation could serve as a diagnostic tool to help doctors distinguish HCL from cancers that have similar features, the study authors wrote. Further research, they noted, is needed to determine the frequency of the V600E mutation in a larger patient group and to clarify whether mutations in other genes may cooperate with BRAF mutations in the development of HCL.

Drugs that target the effects of BRAF mutations are in development, such as vemurafenib (PLX-4032). When the authors treated cells from HCL patients with the BRAF inhibitor PLX-4720, they observed biochemical changes that indicated a reduction in the activity of a growth-promoting pathway. These inhibitors could be tested in patients whose disease does not respond to initial treatment with other agents or who relapse, the authors said.

The study findings are both “unexpected” and “very interesting,” said Dr. Robert Kreitman of NCI’s Center for Cancer Research. “The [V600E] mutation is a potential target for treatment and diagnosis, and it may also play a role in why normal lymphocytes become hairy cells,” added Dr. Kreitman, who leads clinical trials in HCL. (See “Treating Multiply Relapsed or Refractory Hairy Cell Leukemia” and “Eliminating Hairy Cell Leukemia Minimal Residual Disease.”)

NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute