The Zon lab has announced the publication of two major melanoma studies by members and affiliates of the lab in the March 24, 2011 issue of Nature. The cover of the issue (shown left) features a photograph taken by one of the researchers, Yariv Houvras, M.D., Ph.D., of a heavily pigmented zebrafish whose melanocytes express SETDB1 and BRAF(V600E).

The studies:

The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset [abstract]
Using a zebrafish model, researchers established SETDB1 as an oncogene in melanomas with the BRAF(V600E) mutation, which is the most common melanoma mutation. The product of SETDB1 is a histone-methylating enzyme, SETDB1, which is also overactive in several other cancers. This is the first instance of a melanoma oncogene being identified by use of zebrafish, and the gene could prove to be a valuable diagnostic and treatment target.

DHODH modulates transcriptional elongation in the neural crest and melanoma [abstract]
Leflunomide, an arthritis drug that acts as a DHODH inhibitor, decreases melanomas in mice both when used alone and when used in combination with a specific inhibitor of the BRAF(V600E) oncogene. These findings have direct clinical potential as leflunomide might prove to be a useful cancer drug, especially when combined with a BRAF inhibitor.

For more information, please read Children’s Hospital Boston’s press release on the papers.

In the news:

• “Zebrafish offer skin cancer clues” – USA Today, 3/23/11
• “Arthritis drug could help beat melanoma” – Reuters, 3/23/11
• “3 studies offer insights into skin and blood cancers” – Boston Globe, 3/24/11



Spotlight

• From fishtank to bedside

  A new drug that boosts numbers of blood stem cells, originally discovered in zebrafish in the Children’s Hospital Boston lab of Leonard Zon, MD, goes to clinical trial in patients with leukemia and lymphoma. Read more in this feature article.

• Matching melanoma tactic for tactic

  Researchers are uncovering the tricks melanoma stem cells use to resist chemotherapy and immune attacks, and hope to turn them on their head to outsmart the deadly cancer. Read more.

• See-through fish open a window on stem-cell biology

  A transparent zebrafish named Casper, developed by Richard White, MD, in the Zon Lab, allows scientists to watch blood production after bone-marrow transplant, and observe how the stem cells embed and build blood in a living fish. Even individual stem cells can be tracked, something that hasn’t been easy to do in living organisms. Casper is helping scientists understand why some transplants don’t “take,” and working to develop ways to help patients rebuild their blood faster. White is particularly interested in using Casper to understand how melanoma tumor cells, which have stem-like characteristics, metastasize, and spread. Read more and listen to clips from NPR’s “Science Friday” in which Zon and White discuss Casper’s potential.

• The Zebrafish Genome Project

  A complex control network of signals in stem cells and their environment regulates the cells’ unique characteristic of “stemness.” With the help of fast-breeding, easy-to-study zebrafish and genomics techniques, researchers in the Stem Cell Program at Children’s Hospital Boston are comprehensively combing the chromosomes to tease out this network. Understanding it in greater detail could give stem cell biologists a new set of tools to coax the maturation of cells. Read more.