Biologists have assembled an inhibitor molecule for leukemic cells
Denis Strigun, Naked Science
A group of scientists from Finland and China has designed an inhibitor molecule for a protein that accelerates the development of acute T-cell lymphoblastic leukemia (T-ALL). The results of the work are presented in the journal Nature Communications (Zhong et al., ORP4L is essential for T-cell acute lymphoblastic leukemia cell survival).
Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoiesis system, which is expressed in the excessive spread of lymphoblasts. ALL most often affects people in childhood (1-6 years) and adolescence. In the case of the T-linear type of ALL, the carriers of mutations are T-lymphocytes of the immune system: they begin to divide uncontrollably, affecting various organs and forming tumor masses. T-ALL has a low effectiveness of treatment and progresses rapidly.
In the new work, the researchers studied the role of the long form of oxysterol-binding protein 4 (ORP4L) in the development of T-ALL. Early work has shown that this protein is present in some cancer cells. The ORP family of proteins itself is designed to bind to oxysterin – oxidized cholesterol – and is also involved in the transmission of lipids and signals between cellular organelles. The latest analysis led the authors to the conclusion that ORP4L promotes the proliferation of cancer T-lymphocytes.
"ORP4L binds a group of proteins that transmit signals on the cell membrane of cancer cells. This accelerates the release of calcium ions from the endoplasmic reticulum. As a result, mitochondria are able to work at full capacity," said Professor Vesa Olkkonen (in a press release Important signaling pathway for leukemia cells discovered – VM). He added that the signaling pathway is thus based on ORP4L to maintain the intensive energy metabolism of mutant T-lymphocytes and their ability to divide.
To construct the inhibitor molecule, scientists used leukemia cells from patients' blood, as well as a culture of cancer T cells grown in the laboratory. The aim of the work was to learn how to purposefully suppress or over-activate the expression of ORP4L. In addition, the role of the protein was considered in vivo by transferring human ORP4L into the body of immunodeficient mice. The new inhibitor may form the basis of alternative drugs against T-ALL and other types of cancer.
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06.09.2016