The path to leukemia treatment
Key gene found in leukemia
Anna Yudina, "Scientific Russia"
A research team from Lund University in Sweden has identified one of the genes that is responsible for the survival and reproduction of cancer cells in leukemia, according to a press release Key gene in leukemia discovered.
Article by Ramakrishnan et al. CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia published in the journal Cell Reports.
Acute myeloid leukemia is one of the most common forms of blood cancer in adults, is associated with low survival and leads to inhibition of normal blood cell formation.
AML is the result of acquired genetic changes in hematopoietic stem cells and, among other things, affects genes that control cell maturation and growth. Although the disease occurs at any age, including in childhood, older people most often suffer from it.
"It is the leukemia stem cells in the bone marrow that contribute to the development of the disease, and therefore we want to find out which genes control these stem cells. Using special CRISPR gene scissors, we were able to study about 100 genes simultaneously using an animal model. This is the first time we have conducted such a large–scale study," said Markus Yaros, head of the research group at Lund University.
The new method using gene scissors means that researchers can effectively control which gene is turned off, which makes it possible to study the function of the gene and, therefore, better understand how diseases arise. Researchers from Lund have discovered that the CXCR4 gene is necessary for the survival of leukemia stem cells. When they cut off this gene, leukemic stem cells cannot survive, as they are completely dependent on the protein that the gene produces.
"When we turned off CXCR4, it created oxidative stress, and leukemic stem cells turned into cells with a limited lifespan. Oxidative stress occurs due to waste generated when oxygen is converted into energy. This is a process that is well regulated in the cell. But when there is an increase in the amount of waste, it leads to toxicity, which leads to cell death," says Ramprasad Ramakrishnan, the first author of the study.
In normal hematopoiesis, the interaction between the CXCL12 and CXCR4 proteins is important for blood stem cells. In contrast, the research team found that CXCL12 is not necessary for leukemia stem cells, which shows a fundamental difference in the regulation of leukemia stem cells and normal blood stem cells.
"It was surprising that CXCL12 did not matter for leukemia stem cells. This is something that in the long term can be used in the development of new drugs against AML," concludes Ramprasad Ramakrishnan.
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