One of the hallmarks of leukemia is unlimited division of blood progenitor cells that lack the capacity to mature into functional cells. Exploring why these cells fail to mature could help researchers develop new therapies to treat the disease.
A scientist at the University of Texas M.D. Anderson Cancer Center is hoping that her studies on the role of epigenetics in acute myeloid leukemia can aid in developing new treatments for people diagnosed with this deadly disease. Epigeneticist Margarida I. Albuquerque Almeida Santos was recruited in 2015 with the help of a First-Time Tenure-Track Award from CPRIT. She joined the Department of Epigenetics and Molecular Carcinogenesis from the National Cancer Institute where she was a postdoctoral fellow.
Almeida Santos focuses on a type of acute myeloid leukemia common in children and older adults. In this disease, blood cells called blasts multiply but can’t mature into functional blood cells. Patients feel tired and weak and are susceptible to infections. Although some can be treated with chemotherapy and a stem cell transplant, the treatments are toxic and not all patients are eligible.
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One of the hallmarks of leukemia is unlimited division of blood progenitor cells that lack the capacity to mature into functional cells. Exploring why these cells fail to mature could help researchers develop new therapies to treat the disease.
A scientist at the University of Texas M.D. Anderson Cancer Center is hoping that her studies on the role of epigenetics in acute myeloid leukemia can aid in developing new treatments for people diagnosed with this deadly disease. Epigeneticist Margarida I. Albuquerque Almeida Santos was recruited in 2015 with the help of a First-Time Tenure-Track Award from CPRIT. She joined the Department of Epigenetics and Molecular Carcinogenesis from the National Cancer Institute where she was a postdoctoral fellow.
Almeida Santos focuses on a type of acute myeloid leukemia common in children and older adults. In this disease, blood cells called blasts multiply but can’t mature into functional blood cells. Patients feel tired and weak and are susceptible to infections. Although some can be treated with chemotherapy and a stem cell transplant, the treatments are toxic and not all patients are eligible.
Using mouse models, Almeida Santos found an epigenetic regulator that keeps the leukemic cells from maturing. “In the type of acute myeloid leukemia we study, stem cell genes are expressed in a cell that shouldn’t behave like a stem cell,” she says. She found that when she genetically deletes this regulator, the leukemia cells differentiate and mature normally.
“There is a drug we tested that actually inhibits the function of this protein,” she says. “The translation is quite exciting because this drug is already in clinical trials for other kinds of cancers.” Almeida Santos hopes it can also be tested in leukemia, either by itself or in combination with other therapies.
“One of the projects we are working on is a combination-therapy screen with our mouse models and human leukemia cells,” she says. “We hope to find drugs that are already approved, which in combination with the one we already found, would have a stronger or more durable effect against the disease.”
She is also working on a similar epigenetic regulator involved in certain types of lymphoma. Patients with a particular type of genetic mutation have a poor prognosis. But Almeida Santos suspects that an inhibitor currently in development could help these patients. “We found that cells of diffuse large B-cell lymphoma with a specific mutation are very sensitive to this inhibitor,” she says. “These drugs are not in clinical trials but have already been developed.” She hopes her findings will prompt the companies to further advance the drug candidates.
She credits CPRIT’s support for advancing her research far beyond what she would have been able to do otherwise. “Without it, I couldn’t have the fantastic team that I have now, and I would never have had access to all the resources required to develop this work,” she says. “I needed the money to be successful and start my lab and fund my people; that, together with being at the number one cancer center in the world was the perfect combination.”
Almeida Santos received her undergraduate and master’s degrees from the University of Lisbon School of Sciences, in Portugal, and her Ph.D. in immunology from the Medical School at the University of Lisbon. She came to the U.S. as a visiting fellow at the University of Pennsylvania Medical School in 2007 and began her postdoctoral fellowship at the National Cancer Institute of the National Institutes of Health in 2008.
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