Anemia Study Identifies Mechanism of Blood Stem Cell Differentiation

by Chrisy Ngilneii on Mar 21 2018 10:37 PM
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  • Ribosomes are linked to blood cells differentiation.
  • Molecular lesions underlying diamond-blackfan anemia reduce ribosome levels in hematopoietic cells.
  • Diamond-Blackfan anemia causes low red blood cells count.
A study of Diamond-Blackfan anemia finds the mechanism that drives the development of mature red blood cells from the earliest form of blood cells, called hematopoietic (blood-forming) stem cells.
Ribosomes and red blood cells
The research team finds that cellular machines called ribosomes are linked to blood stem cell differentiation. Ribosomes are the protein builders in the cells.

Diamond-Blackfan anemia (DBA) occurs when the bone marrow does not make sufficient red blood cells necessary for carrying oxygen from the lungs to other parts of the body. This makes the patient severely anemic. This kind of anemia is not due to insufficiencies in iron, vitamin B12, folate or erythropoietin. DBA is a life threatening condition leading to other potential abnormalities. DBA affects approximately 5 to 7 per million live born infants worldwide.

It was first described in 1938 by Louis Diamond and Kenneth Blackfan. Then, nearly 30 years ago, Stuart Orkin, MD, also of Boston Children's, reported that a protein called GATA1 is a key factor in the production of hemoglobin. Recently, other studies have revealed that genetic analysis has revealed that some patients with Diamond-Blackfan have mutations that block normal GATA1 production.

According to previous studies, many patients with Diamond-Blackfan anemia have mutated ribosomal protein genes and only the maturation of red blood cells is impaired.

Ribosomes and the protein GATA1
The research team studied human cell samples from patients with Diamond-Blackfan anemia and finds that the quantity of ribosomes within blood cell precursors directly influences their ability to produce effective levels of GATA1, which is needed for hemoglobin production and also for red blood cell production.

Now the team has definitively found that a reduced number of ribosomes slashes the output of GATA1 proteins inside blood stem cells, therefore impairing their differentiation into mature red blood cells.

According to the research team, the presence of GATA1 proteins in early blood stem cells helps prime them for differentiation into red blood cells. Without enough ribosomes to produce enough GATA1 proteins, these early cells simply never receive the signal to become red blood cells.

"This raises the question of whether we can design a gene therapy to overcome the GATA1 deficiency," Sankaran, the author of the study says. "We now have a tremendous interest in this approach and believe it can be done."

"I think what's great is that we can learn about developmental biology just by looking at our own patients very carefully," says Sankaran. "Genetic errors can give us the chance to pick apart the complex pieces of health and discover how they relate to one another."

Treatment for Diamond-Blackfan Anemia
Treatment options for DBA include:
  • Corticosteroid therapy – which is used in children above 12 months. This can improve the red blood cell count. The usual steroid is prednisone. Steroids act as bone marrow stimulants. Low doses are maintained to avoid side effects.
  • Blood transfusion therapy – used when anemia is severe and the individual does not respond to steroids.
  • Hematopoietic stem cell transplantation (HSCT) – is the only curative for DBA. HSCT involves transplanting a person’s healthy stem cells. This is not an easy option for most people. The success rate depends on a number of factors including matching factors (matched siblings, complete tissue match).
Individuals with DBA are usually evaluated by haematologists, clinical geneticists, cardiologists, nephrologist and urologist (as required) and medical genetics counsellors. A multidisciplinary approach is critical to manage DBA and keep secondary complications in check.

  1. Rajiv K. Khajuria, Mathias Munschauer et al. Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis, Cell DOI: