A team from the Autonomous University of Madrid (UAM) and the Jiménez Díaz Foundation has published a series of literature reviews that highlight the roles of the Hedgehog, Notch and Wnt signaling pathways in the chemoresistance of leukemic stem cells.
The Experimental Hematology group belonging to the Jiménez Díaz Foundation Health Research Institute and the Autonomous University of Madrid (UAM) have summarized, in a series of recent bibliographic reviews published in first-quartile journals, the most crucial roles of Hedgehog signaling pathways. , Notch and Wnt in chemoresistant cells of acute myeloid leukemia.
Acute myeloid leukemia is a type of hematological cancer that prevents the proper development of blood cells. This cancer originates in the leukemic stem cell, a cell that has the ability to remain in an inactive phase, called quiescence. This characteristic makes it resistant to chemotherapy, since it is not in the cell division stage.
This is believed to be the cause of relapse in this disease, since chemotherapy would eliminate most of the tumor cells, but not those in this quiescent phase. This state is regulated by signaling pathways highly conserved in nature, such as the Hedgehog, Notch and Wnt pathways.
Under the premise of adequately understanding the role of these signaling pathways in the leukemic stem cells of acute myeloid leukemia, researchers Daniel Láinez González and Juan Manuel Alonso Domínguez have reviewed the current knowledge on the subject.
The role of signaling pathways in cellular quiescence
In the articles published in the journals Biology and Cancers , the authors begin by presenting the pathways to be examined, and then explain their role in normal hematopoiesis and hematological malignancies, with special emphasis on acute myeloid leukemia. In this way, the reader can clearly understand the differences between both scenarios.
Subsequently, clinical trials in acute myeloid leukemia that target these signaling pathways are reviewed, highlighting their usefulness for the disease under study.
Finally, a discussion is opened that shows that these signaling pathways play a key role in the entry into the cell cycle of leukemic stem cells and, therefore, lead to chemoresistance to current medications.
“More experiments are required to reach a unified conclusion,” the authors say. “This is because, although the studies reviewed agree on the importance of the pathways, it is still not clear whether the inhibition of quiescence, which allows entry into the cell cycle, is due to the activation or inhibition of the pathways. Hedgehog, Notch or Wnt.”
In fact, this is precisely the question that part of this Experimental Hematology group at the Jiménez Díaz Foundation is currently working on: “We are inhibiting these pathways with drugs to study the quiescence of leukemic stem cells and verify if the percentage of cells in This phase decreases when the signaling pathways are deactivated.”
In conclusion, the study of Hedgehog, Notch and Wnt signaling pathways is crucial to understand the resistance of leukemic stem cells to chemotherapy. Future findings in this direction could open a new path towards more effective treatments that are less associated with relapses in this devastating disease.
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Bibliographic reference:
Láinez-González, D.; Alonso-Aguado, AB; Alonso-Dominguez, J.M. (2023). Understanding the Wnt Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Feasible Key against Relapses . Biology , 12, 683. doi.org/10.3390/biology12050683
Láinez-González, D.; Serrano-López, J.; Alonso-Dominguez, J.M. (2022). Understanding the Notch Signaling Pathway in Acute Myeloid Leukemia Stem Cells: From Hematopoiesis to Neoplasia . Cancers , 14, 1459. doi.org/10.3390/cancers14061459
Láinez-González, D.; Serrano-López, J.; Alonso-Dominguez, J.M. (2021). Understanding the Hedgehog Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Necessary Step toward a Cure . Biology , 10, 255. doi.org/10.3390/biology10040255
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