creating a
healthier future

Award-winning i3S works on acute myeloid leukemia

PhD students Marta Lopes and Joana Reis, who work in the “Hematopoiesis & Microenvironments” group under the guidance of researcher Delfim Duarte, recently won travel grants worth 500 euros awarded by the European Hematology Association to present their work at the association’s annual congress, which takes place in Madrid from June the 13th to the 16th.

Both have focused their research on the study of acute myeloid leukemia (AML), an aggressive hematological cancer caused by the uncontrolled proliferation of myeloid progenitor cells in the bone marrow and blood. This disease has a poor prognosis and therapeutic options are limited, as chemotherapy is associated with several complications, namely infection and very slow recovery, and bone marrow transplantation has a very high mortality rate.

Marta Lopes, student in the Doctoral Program in Biomedical Sciences at the Abel Salazar Institute of Biomedical Sciences (ICBAS), studied the role of transferrin, a protein produced by the liver whose function is to transport iron to the marrow, spleen, liver, and muscles, and which is present at increased levels at the time of AML diagnosis. It was found that induction chemotherapy increases iron levels even further, in addition to being associated with the appearance of free iron, which is toxic to the bone marrow microenvironment and favors bacterial proliferation. The team that Marta Lopes is part of then decided to evaluate the impact of transferrin combined with chemotherapy on the response to AML.

Using an animal model with AML and human AML cell lines, the researcher concluded that the combined treatment of chemotherapy and transferrin decreases the number of AML cells, reduces the levels of toxic free iron, and increases the survival of mice. She also observed a significant increase in the survival of mice with E. coli infection that received transferrin.

These results, explains Marta Sofia Lopes, “are very important and open the door to a potential new therapy for AML, because they show that the combination of chemotherapy with transferrin has an anti-leukemic and protective effect in the context of the infection”.

Increasing the success rate of bone marrow transplants

Joana Reis, a student in the Doctoral Program in Molecular and Cellular Biology at ICBAS/FCUP/i3S, has been studying possible determinants for the success of bone marrow transplants, which are used to treat patients with AML and other conditions. These patients, due to chemotherapy or repeated blood transfusions, often have high levels of iron in circulation, which is a poor prognostic factor for transplantation.

Since iron overload leads to the production of oxidants, Joana Reis focused on the possibility that the expression of a transcription factor involved in protection against oxidative stress, Nrf2, is decisive for the success of bone marrow transplantation. She then found that “mice that do not express the transcription factor have a very short survival after transplantation when overloaded with iron, indicating that the expression of this protein is crucial for the success of the transplant”.

The team also focused on trying to understand the cell type that determines post-transplant survival, having identified a cell type of stromal cells, mesenchymal stem cells.

This study, highlights Joana Reis, “has the potential to increase the success rate of transplants, since there are genetic variants of Nrf2 in the population, which can contribute to the stratification of patients before transplantation, using, for example, therapies that eliminate the iron in patients at increased risk, thus reducing associated mortality”.

Subscribe to our newsletter and keep up to date with our latest achievements.