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Antihistamines Show Potential to Destroy Leukemic Stem Cells

BARCELONA (ESP), September 2019 — Ruth M. Risueño, Ph.D., leads the leukemic stem cell group of the Josep Carreras Leukaemia Research Institute. This group investigates acute myeloid leukemia (AML) and the cell population responsible for the disease spreading, persisting and, if it has been treated and overcome, reappearing.

AML has a poor prognosis. Its treatment with chemotherapy has a high rate of recidivism. This relapse may be because a small number of diseased stem cells have become resistant to treatment, so it is only a matter of time before they start to spread.

Leukemic stem cells can be renewed or differentiated. They replicate themselves indefinitely to maintain their population. However, when they differentiate, they generate all the types of mature leukemic cells found in the tumor. These adult cells are more sensitive to chemotherapy.

"If we can differentiate all leukemic stem cells, this population would be depleted. Therefore, its ability to maintain the disease and the chances of regeneration and relapse would be lost," said Dr. Risueño.

The research recently published in EBioMedicine, in which Dr. Risueño collaborates with doctoral student Josep Maria Cornet-Masana, details the first phase of screening of molecules by computer and unearthing a group of antihistamines that, in tests in laboratory samples and mice, resulted in differentiation induction. 

Through a mechanism that is different from their antiallergic function, antihistamines penetrate two vital "organs" of the cell — mitochondria, which are responsible for metabolizing energy, and lysosomes, responsible for cell digestion — causing their failure and leading to cell death.

"This does not affect healthy cells because the process of transforming leukemic cells implies that mitochondria and lysosomes are more fragile. This fact allows them to have more resistance to pre-apoptotic stimuli — that is, to the cell's safety mechanisms that cause their death when something goes wrong, and increase the metabolic rate, which is necessary for all tumor cells.

“What is an advantage for the propagation of the tumor becomes a disadvantage for its protection against such drugs," said Dr. Risueño.

Currently, these drugs cannot be used against leukemia because of their rapid degradation and because they do not have a direct administration technique on diseased cells. Dr. Risueño's team is working to make these drugs more stable while developing a mechanism so they can be administered directly and distinctively on leukemic stem cells.

Learn more:
http://www.carrerasresearch.org/en/discovered-the-potential-of-a-group-of-antihistamines-that-cause-the-death-of-leukaemic-stem-cells_126171
DOI: https://doi.org/10.1016/j.ebiom.2019.08.021