Iron-restricted anemias – which are characterised by a lack of red blood cells – leave millions of people weak, tired and unable to concentrate.
New research by the University of Virginia School of Medicine sheds light on the process that causes the body to create insufficient numbers of these vital red blood cells, and could lead to new treatments for the condition.
The previously unknown clockwork mechanism within the body that controls the creation of oxygen-carrying red blood cells was discovered by Shadi Khalil, one of the study’s authors, during an examination of bone marrow cells.
He noticed that the cells contained large pools of the receptor for erythropoietin, a hormone that directs the bone marrow to make red blood cells.
To do its job receiving the instruction to make blood cells, the receptor must be on the outside of the marrow cells, yet a lot of it was stored inside them.
This partly explains why some people’s bone marrow cells fail to follow the hormone’s instructions.
Another researcher on the project, Lorrie Delehanty, was studying anemia using a model the lab developed called anemia in a dish.
‘If you drop the iron level way down, these cells act like anemic cells. They basically become anemic cells – they even look very pale,’ she said. She also noticed the disappearance of a particular protein called Scribble.
The Scribble protein (named after the SCRIB gene that produces it) proved to be a key piece of the clockwork mechanism. The amount of iron in the blood affects the amount of the Scribble protein available, and Scribble controls whether the hormone receptor is welled up inside the bone marrow cells or doing its job on the outside.
‘We realised that this was kind of a complicated symphony that starts with iron and ultimately controls how much and what kind of messages the cells get,’ Khalil said.
The researchers used this knowledge to fix EPO resistance in their model, and they hope the discovery will eventually be useful for treating anemias in people, too. The research has been published in the Journal of Experimental Medicine.