Italian scientists reveal genetic root of rare form of leukaemia

In collaboration with Adfero

Using cutting-edge DNA sequencing, Italian scientists have identified the underlying gene fault in a rare form of blood cancer called hairy-cell leukaemia (HCL), according to a paper published in the New England Journal of Medicine.

The finding will allow doctors to quickly and accurately diagnose the disease, for which treatments are available, but which can be hard to tell apart from several other rare forms of leukaemia.

The researchers, based at the at the University of Perugia, used a technique known as massively parallel sequencing to sequence the genome of a patient with HCL, and then compared the results with other patients with the disease.

They identified five faults that were present in the original patient's HCL cells but not his healthy ones, including a well-known fault in the BRAF gene (called V600E). The link between BRAF and cancer was originally discovered by Cancer Research UK-funded scientists working at the Institute of Cancer Research.

The BRAF gene affects how cells divide and grow and is known to be faulty in many types of cancer, including up to seven out of ten malignant melanomas.

The researchers then used conventional 'Sanger' sequencing to verify this finding in cells taken from 47 further HCL patients and 195 patients with other types of leukaemia or lymphoma.

They found that the same BRAF fault was present in all 47 patients, but in none of the patients with other types of blood cancer.

This suggests that by analysing BRAF faults, it may be possible to determine whether a patient has HCL or a different type of lymphoma, and therefore decide the best course of treatment.

The researchers then grew HCL cells with BRAF faults in the laboratory and treated them with an experimental drug called PLX-4720, which is designed to target and block the growth of cells containing the damaged BRAF gene.

Treatment with PLX-4720 led to a decrease in the activity of two signalling proteins called MEK and ERK, which play a major role in regulating cell growth, and are thought to be involved in the survival of HCL cells.

The finding suggests that patients who have not responded well to standard therapies may benefit from taking a drug that targets the BRAF fault in their HCL cells.

Drugs such as these are currently the subject of several clinical trials, including a recent Phase III trial of an anti-BRAF drug called vemurafenib in melanoma patients.

Writing in the New England Journal of Medicine, the study authors concluded: "The BRAF V600E mutation was present in all patients with HCL who were evaluated.

"This finding may have implications for the pathogenesis, diagnosis and targeted therapy of HCL."

Dr Fiona Hemsley, head of strategic projects at Cancer Research UK said: “Not only is this work important for people affected by hairy-cell leukaemia, but it also shows the incredible potential of next-generation DNA sequencing technologies to crack the cancer code.

“We’re now entering an exciting era of genomics, and we expect to see many more advances like this from DNA sequencing projects. Cancer Research UK plans to capitalise on these advances in sequencing technology.”


  • Tiacci E, et al, BRAF Mutations in Hairy-Cell Leukemia, N Engl J Med 2011; 364:2305-2315 DOI: 10.1056/NEJMoa1014209