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St. Jude, Collaborators Awarded $15M NIH Grant to Support Leukemia Genomic Research


NEW YORK (GenomeWeb) – The National Institutes of Health this month committed roughly $15 million over five years to St. Jude Children's Research Hospital and several collaborating institutions to support their research into how genomic variability influences the treatment of acute lymphoblastic leukemia (ALL).

With the funding, the partners have formed the Center for Precision Medicine in Leukemia (CPML), which is specifically tasked with identifying the mechanisms underlying the differential responses among pediatric and adult ALL patients to therapy.

According to Mary Relling, a St. Jude researcher and co-principal investigator for the CPML, ALL is the most common pediatric cancer, accounting for about a third of all childhood malignancies. The disease is also viewed as a success story in oncologic medicine, she told GenomeWeb, noting that the survival rate for the disease has improved from around 5 percent in the 1960s to over 90 percent currently — in part due to the use of genetic analysis to help guide patient treatment.

For example, in 2009, St. Jude researchers identified genetic mutations behind an aggressive subtype of ALL that does not respond well to standard chemotherapies.

Through the CPML, Relling said, St. Jude and its collaborators hope to "apply the same principles that we've applied to pediatric ALL to adult ALL to improve cure rates." At the same time, the center will try to understand if there is a genetic basis to the higher drug resistance observed in adult ALL patients compared with pediatric ones.

In addition to St. Jude, the CPML also includes investigators from the HudsonAlpha Institute for Biotechnology; the University of California, San Francisco; the Children's Hospital of Philadelphia; the University of Florida; Nationwide Children's Hospital; the University of Chicago; Montefiore Medical Center; the University of New Mexico; MD Anderson Cancer Center; and Erasmus University.

Overall, the groups comprising the CPML have all been collaborators for many years, Relling explained, but a lack of funding has limited their interactions. The NIH grant will "allow us to cement our interactions," while providing the resources necessary to keep track of patient samples and the work each of the center's investigators is undertaking.

Even in projects involving a small number of researchers, "it can be a challenge to keep track of whose doing what with everything," she said. "We have been struggling with that over the past couple of years. One of the great things about getting this money" will be to develop an infrastructure to address this issue.

The funding, Relling added, will also enable CPML scientists to run studies with hundreds of samples rather than just dozens, helping to eliminate bias and enabling population-based assessments of ALL.

The CPML has three overarching aims, the first of which is to elucidate the genomic basis for interpatient differences in response to chemotherapy, she said. This will include examining genome variation among ALL subtypes and identifying the inherited and somatically acquired variation associated with treatment response.

"This [effort] also includes a comparison of how the genomics might differ in adults versus kids," Relling noted.

The second main goal of the center is to uncover genomic variation associated with de novo and acquired drug resistance in primary ALL cells from pediatric and adult patients at diagnosis and at relapse, as well as to elucidate the mechanisms by which this variation influences drug resistance and treatment response in these two patient populations.

The CPML's final goal is to understand the role genomics plays in the different adverse effects ALL therapies can have in some patients but not others, including between adults and children with the disease.

While the center's work is expected to benefit ALL patients specifically, Relling said that it could also positively impact those suffering from unrelated conditions.

"We use eight to 10 different medications to cure ALL, and several of those are more commonly used to treat other diseases that aren't cancer," she said. "For example, steroids … that are essential to curing ALL are very widely used for allergy conditions, arthritis, and other kinds of autoimmune [disorders].

"The discoveries we make in patients with ALL, at least in terms of genomics-related side effects, will have implications for lots of adult and other pediatric populations outside of leukemia," she said.