Stories about: Diamond Blackfan anemia

Discovering a rare anemia in time to save an infant’s life

Illustration of the erythropoietin hormone. A newly-discovered genetic mutation, which switches one amino acid in EPO's structure, resulted in two cases of rare anemia.
An illustration showing the structure of a cell-signaling cytokine called erythropoietin (EPO). It has long been thought that when EPO binds with its receptor, EPOR, it functions like an on/off switch, triggering red blood cell production. New findings suggest that this process is more nuanced than previously thought; even slight variations to cytokines like EPO can cause disease.

While researching a rare blood disorder called Diamond-Blackfan anemia, scientists stumbled upon an even rarer anemia caused by a previously-unknown genetic mutation. During their investigation, the team of scientists — from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, the Broad Institute of Harvard and MIT and Yale University — had the relatively unusual opportunity to develop an “on-the-fly” therapy.

As they analyzed the genes of one boy who had died from the newly-discovered blood disorder, the team’s findings allowed them to help save the life of his infant sister, who was also born with the same genetic mutation. The results were recently reported in Cell.

“We had a unique opportunity here to do research, and turn it back to a patient right away,” says Vijay Sankaran, MD, PhD, the paper’s co-corresponding author and a principal investigator at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “It’s incredibly rewarding to be able to bring research full circle to impact a patient’s life.”

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Stem cell workaround cracks open new leads in Diamond Blackfan anemia

Diamond Blackfan anemia iPS cells hematopoietic progenitor cells
Though not bona-fide stem cells, hematopoietic progenitor cells produce red blood cells when exposed to certain chemicals. Could some of these compounds lead to new drugs for Diamond Blackfan anemia?

Diamond Blackfan anemia (DBA) has long been a disease waiting for a cure. First described in 1938 by Louis K. Diamond, MD, of Boston Children’s Hospital and his mentor, Kenneth Blackfan, MD, the rare, severe blood disorder prevents the bone marrow from making enough red blood cells. It’s been linked to mutations affecting a variety of proteins in ribosomes, the cellular organelles that themselves build proteins. The first mutation was reported in 1999.

But scientists have been unable to connect the dots and turn that knowledge into new treatments for DBA. Steroids are still the mainstay of care, and they help only about half of patients. Some people eventually stop responding, and many are forced onto lifelong blood transfusions.

Researchers have tried for years to isolate and study patients’ blood stem cells, hoping to recapture the disease process and gather new therapeutic leads. Some blood stem cells have been isolated, but they’re very rare and can’t be replicated in enough numbers to be useful for research.

Induced pluripotent stem (iPS) cells, first created in 2006 from donor skin cells, seemed to raise new hope. They can theoretically generate virtually any specialized cell, allowing scientists model a patient’s disease in a dish and test potential drugs.

There’s been just one hitch. “People quickly ran into problems with blood,” says hematology researcher Sergei Doulatov, PhD. “iPS cells have been hard to instruct when it comes to making blood cells.”

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