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Jun 05

Interdisciplinary Leukemia Project Aids in Important Cancer Genomics Discovery

Too often, it is difficult to get a feel for how much difference a single grant can really make.  Cancer science is cumulative, with the work of one scientist building on that of another, and it can be difficult to identify real breakthroughs in the fight against cancer until we have some hindsight. But sometimes, we get lucky. In 2008, the Cancer Research Foundation committed $3 million dollars to support the Interdisciplinary Leukemia Project and we are excited to announce that recently members of the project announced a major discovery, proving the concept of team science and providing real insight into how cancer can develop.

The Interdisciplinary Leukemia Project was designed to knit together a number of different ongoing research projects, all focused on therapy based leukemia, a secondary cancer thought to be caused, at least in part, by the treatments patients received to put their primary disease into remission.  One expectation was that looking at a single disease from the viewpoints of a number of different scientific disciplines would provide new ideas about how cancer develops and who might be at greater risk.  Additionally, we hoped that the project would create real insight into how to better personalize cancer treatments, with a hope of significantly reducing secondary cancers, as well as reducing harmful side effects from treatment. Finally, there was the possibility that by creating interaction among teams from different disciplines, we would accelerate the scientific process, creating feedback loops among the groups and making individual experiments more efficient. 

Now, we are pleased to let you know of a major discovery arising out of that ongoing project. Kevin White, PhD and Meghan McNerny, MD PhD recently announced the identification of CUX1, a single gene whose absence or alteration appears to be critical in the development of many forms of blood cancer.  Kevin White is the Director of the Institute for Genomics and Systems Biology and is one of the project leaders in charge of examining the leukemia genome; Meghan is a pathologist working in Kevin's laboratory. Meghan was able to identify CUX1 by partnering her work regarding genetics and the genomes of specific cohorts of leukemia patients with the bioinformatic computing power also included in the Interdisciplinary Leukemia Project. CUX1 is a single gene located on the seventh chromosome; it caught Meghan's interest because its expression was most significantly different in the genomes of the group of patients with leukemia Meghan was studying.  Meghan then teamed up with other members of the project to remove the gene in generations of fruit flies, and then in mice.  In both cases, the removal of CUX 1 led to the development of leukemia.

Everyone involved in the Cancer Research Foundation is delighted about Meghan's discovery.   The identification of the CUX1 gene suggests that it could be an important target for therapies that could stop the production of leukemia cancer cells and even prevent the occurrence of the disease. 

Perhaps even more satisfying is that Meghan's discovery is built on the past discoveries of other CRF funded scientists.  In the early 1970's, Dr. Janet Rowley described a majority of cases of certain leukemias exhibited the loss of part of the 7th chromosome. This discovery, partly funded by the CRF, led to the current understanding of cancer as a genetic disease. Ten years later,  Michelle LeBeau, herself trained by Janet Rowley and a recipient of the CRF's Young Investigator Award early in her career, put to work new technologies which allowed her to better target which part of chromosome 7 contained the leukemia effect.  This allowed her to narrow in on the culprit, which allowed her to limit the genetic cause to 50 possible genes.  Meghan, starting in 2009, picked up Dr. LeBeau's findings and used next generation genomic sequencing and "Big Data" computing to identify CUX1.

The next step is to investigate how CUX1 regulates other genes in the hope of finding pathways that can be influenced by drugs, and there is high hope that this discovery will provide important insight and real potential treatments for leukemias and other deadly cancers. The discovery of this particular gene, with its direct connection to leukemia development, is another strong step in the battle against cancer and the CRF is proud to be part of it.