- 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.
The research team finds that cellular machines called ribosomes are linked to blood stem cell differentiation. Ribosomes are the protein builders in the cells.
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.
"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."
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).
References:
- Rajiv K. Khajuria, Mathias Munschauer et al. Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis, Cell DOI: https://doi.org/10.1016/j.cell.2018.02.036
Source-Medindia