Recognizing the expertise, proven success record and promise of further discovery, the Leukemia & Lymphoma Society (LLS) has awarded a Specialized Center of Research (SCOR) grant to a 12-member team of researchers at Sylvester Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center (MSKCC), and Brigham and Women’s Hospital (BWH). The team, led by Stephen D. Nimer, M.D., director of Sylvester, is focused on advancing knowledge of the epigenetic basis of cancer and using this knowledge to develop new therapies for a variety of myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms.
Other Sylvester investigators include Ronan T. Swords, M.D., Ph.D., Maria Figueroa, M.D., Ramin Shiekhattar, Ph.D., Mingjiang Xu, M.D., Ph.D., Feng-Chun Yang, M.D., Ph.D., Sion Williams, Ph.D., Steven Chen, Ph.D., and Arthur Zelent, Ph.D. Together with their collaborators at MSKCC and BWH, they will focus on unlocking the epigenetic mechanisms involved in the abnormal growth that characterizes myeloid cancers. This will involve the development of complex but accurate preclinical models to evaluate potential genes of interest, and then develop and test therapeutic strategies for people diagnosed with these cancers.
Myeloid malignancies such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN) arise due to a combination of genetic mutations and epigenetic abnormalities that sustain the abnormal behavior of cancer cells. The genetic material of the cell is the “hard drive” full of instructions that allow cells to grow, have unique functions, and ultimately live or die. Epigenetics is the “software” of the cell, allowing access to the information from the hard drive in a controlled manner. This interplay between the hardware and the software culminates in gene expression, allowing the genetic material to be read and interpreted.
“While we have learned a lot about how individual cancer-causing genes affect these epigenetic factors, we are only now learning how combinations of abnormal genes alter the epigenetic landscape and contribute to the abnormal identity that cancer cells assume,” said Nimer. “We have drugs that can reverse some of these changes, but we need both to develop new drugs as well as to learn how to combine these epigenetic-focused drugs in order to cure more cancers.”
This $5 million LLS SCOR grant will hasten progress on that front and cement the collaborations among these leading experts.
Maria Figueroa, M.D., a key member of the research team, said, “We will work in concert to investigate new concepts in epigenetic therapies, gain a greater understanding of how multiple mutations can drive epigenetic regulation of gene expression, and illuminate and modify the clinical behavior of myeloid malignancies.”
The SCOR researchers plan to generate additional unique models of human myeloid malignancies and share those new models with the greater cancer research community, including Leukemia & Lymphoma Society researchers.
Overall, the SCOR has been assembled to take advantage of the synergies and complementary expertise of the investigators involved. Working together, they will provide state-of-the-art animal modeling, existing and developing epigenetic technologies, a large clinical volume, and a vast sample repository to investigate new concepts in epigenetic therapies.
“Our ultimate goal,” said Nimer, “is to maximize this SCOR grant to accelerate epigenetic advances in the treatment of myeloid malignancies.”