Genes, hormones and red blood cell formation

Source: WAIMR

A new understanding of how red blood cell production is controlled could lead to improvements in the treatment of anaemia, according to West Australian medical researchers.

The findings are reported in two papers published in Blood, the journal of the American Society of Hematology, by a group of Australian scientists, led by Western Australian Institute for Medical Research (WAIMR) director Peter Klinken and his laboratory for cancer medicine.

One of the papers, 'Hls5 regulated erythroid differentiation by modulating GATA-1 activity', shows how the gene Hls5, which was discovered by Klinken's team, affects red cell production.

"We have established that Hls5 impedes the maturation of immature red blood cells which has provided us with a much better understanding of what Hls5 does and how it is linked with the development of leukaemias and cancers," he said.

"Another arm of our research has revealed that thyroid hormone, which it was already established affected metabolism, also contributes to red blood cell formation - which was previously unknown."

Klinken said both findings opened the door to exploring new ways of treating a range of anaemias.

"Anaemias develop where a person's blood is low in red blood cells so the two discoveries we have made may provide an insight into how to turn these conditions around," he said.

"Our findings indicate that minor changes in Hls5 levels can have a big impact and so the possibility of modulating this gene to generate new treatments is significant.

"As a number of patients don't respond to erythropoietin (EPO) - the current form of hormone therapy for anaemias - this new knowledge will hopefully lead to alternative treatments."

The research being conducted by Klinken and his team is funded by the National Health and Medical Research Council and Perth biotech BioPharmica.

The papers are: Raelene Endersby, Ian J. Majewski, Louise Winteringham, Jennifer G. Beaumont, Amy Samuels, Robin Scaife, Esther Lim, Merlin Crossley, S. Peter Klinken, and Jean-Philippe Lalonde, 'Hls5 regulated erythroid differentiation by modulating GATA-1 activity', Blood, Feb 2008; 111: 1946 - 1950.

Tulene S. Kendrick, Christine J. Payne, Michael R. Epis, Jessica R. Schneider, Peter J. Leedman, S. Peter Klinken, and Evan Ingley, 'Erythroid defects in TR-/- mice', Blood, Jan 2008; doi:10.1182/blood-2007-07-101105.