Patients with bone marrow disorders can develop an impaired production of healthy red blood cells, resulting in anemia. As a result, these patients require regular blood transfusions. However, this can lead to serious health complications due to elevated iron levels, which are released from red blood cells at the end of their lifespan. The body is unable to remove excess iron caused by repeated blood transfusions. Therefore, elevated iron levels must be treated with medication, as they can cause severe tissue toxicity and lead to cardiac arrest; treatment is often accompanied by side effects such as nausea, diarrhea, vomiting, fever, and headache. To develop new strategies for treating anemia, we studied stress erythropoiesis. Stress erythropoiesis entails the emergency production of red blood cells in response to anemia. An improved understanding of stress erythropoiesis, therefore, may lead to the identification of signals that we can stimulate to enhance erythropoiesis in patients with chronic anemic conditions, thereby reducing the need for blood transfusions.
There are, however, limited insights into the molecular processes that regulate stress erythropoiesis in the bone marrow. In the bone marrow, we found that the protein E-cadherin is specifically expressed in red blood cell precursors and that its expression increases in response to anemia (1, 2). Outside the bone marrow, E-cadherin helps cells to connect, which is essential for tissue organization.
We demonstrated that under healthy conditions, E-cadherin expression by erythroid precursor cells is not necessary for their growth or differentiation into red blood cells. However, in response to anemia, our research found that E-cadherin promotes the rapid differentiation of erythroid precursor cells into red blood cells (2). Moreover, we revealed that in the bone marrow, the response to anemia occurs in two phases: first, an expansion of erythroid precursor cells, followed by a second phase of accelerated differentiation into red blood cells. These findings provide a foundation for future research to improve understanding of the molecular mechanisms behind the identified response waves to anemia that are triggered in the bone marrow. Overall, to develop novel treatment options to treat anemia in patients with chronic anemic conditions.
1. https://doi.org/10.3390/biom12111706
2. https://doi.org/10.1182/bloodadvances.2025017433