Mutations in JAK3 gene identified in subtype of lymphoma provide potential drug target

June 15, 2012

A substantial proportion of NK/T-cell lymphomas harbor Janus Kinase 3 gene mutations. Patients with these lymphomas might benefit from treatment with a Janus Kinase inhibitor according to a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

"Very little was known about the genetic and molecular defects causing NK/T-cell lymphoma before we started this work," said Bin Tean Teh, M.D., Ph.D., director of the National Cancer Center Singapore-Van Andel Research Institute Translational Research Laboratory at the NCCS, and professor at the Duke-NUS Graduate Medical School in Singapore. "There is no effective treatment and this type of cancer carries an extremely .

"It is tremendously rewarding to have identified genetic mutations that appear to have an important role in driving the cancer in a considerable fraction of cases. Moreover, we are excited that there is a drug already in phase III trials for the treatment of rheumatoid arthritis that targets the . We are in the process of planning a clinical trial to study whether this drug benefits NK/T-cell ," said Teh.

NK/T-cell lymphoma is a very aggressive form of lymphoma. It is particularly prevalent in Asia.

"Many years ago, I and a colleague came to the Van Andel Research Institute in Grand Rapids, Mich.," said Teh. "My colleague unfortunately developed NK/T-cell lymphoma and passed away. It was the only case of this cancer ever diagnosed in Grand Rapids. As this illustrates, it is a relatively rare subtype of lymphoma in the United States, but it is responsible for the deaths of a large number of people in Asia, in particular in China and Korea. It accounts for almost half of all T-cell lymphomas in some parts of Asia.

"The passing of my colleague, whom I was very close to, was the reason that I started studying NK/T-cell lymphoma. It has been a complicated puzzle, but I feel that we have pieced together enough that we will have an impact on a large number of patients with this disease."

To identify that might have a functional consequence, Teh and his colleagues sequenced all the genes in NK/T-cell lymphoma cells from four patients. In addition to mutations in genes known to be associated with cancer, they detected mutations in the Janus Kinase 3 (JAK3) gene in the cancer cells from half of the patients. The researchers conducted follow-up sequencing of NK/T-cell lymphoma cells from an additional 65 patients and identified JAK3 mutations in 23 of those patients.

The mutations enabled NK/T-cell lymphoma cell lines to grow in culture in the absence of the normally essential growth factor IL-2. This meant that the mutations caused dysregulated activation of JAK3, and suggested that JAK3 might be a good drug target.

Consistent with this idea, a JAK inhibitor that is currently being assessed in phase III clinical trials as a treatment for killed cultured NK/T-cell lymphoma cell lines by a process known as apoptosis.

"We are currently putting together a proposal to test JAK inhibitors as a treatment for NK/T-cell with JAK3 ," said Teh. "I am hopeful that we might have found a molecular target for the treatment of a least some patients with this otherwise fatal disease."

Explore further: Fighting cancer with the immune system

Related Stories

Fighting cancer with the immune system

June 11, 2012
The human immune system has a natural ability to identify and attack tumor cells. Natural killer (NK) cells are innate immune cells that are particularly effective at killing tumor cells due to their ability to secrete cytotoxic ...

New potential therapeutic target identified for Diffuse Large B-Cell Lymphoma

November 28, 2011
Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have discovered a new potential therapeutic target for Diffuse Large B-Cell Lymphoma (DLBCL), the most aggressive and ...

Recommended for you

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

Searching for the 'signature' causes of BRCAness in breast cancer

August 21, 2017
Breast cancer cells with defects in the DNA damage repair-genes BRCA1 and BRCA2 have a mutational signature (a pattern of base swaps—e.g., Ts for Gs, Cs for As—throughout a genome) known in cancer genomics as "Signature ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.