Two new studies that could ultimately help with the diagnosis and treatment of leukemia were published in the Sunday edition of the journal Nature Genetics.
In the first, a team of scientists from the Center for Cancer Biology (CCB) at the University of Australia and the University of Washington discovered a genetic defect that they says indicates a pre-disposition to contract acute myeloid leukemia and myelodysplasia.
According to a University of Washington press release, those mutations were discovered in the GATA2 gene, which they say acts as a “master control” in the formation of white blood cells.
Leading the research were Dr. Hamish Scott and Dr. Richard J. D’Andrea at the University of Australia, and Dr. Marshall Horwitz, a professor of pathology and a genetic medicine practitioner at the UW Medical Center in Seattle.
According to the press release, “The genetic mutation was first discovered in a patient from central Washington. The research participant had been successfully treated for leukemia in 1992 through a bone marrow transplant at UW Medical Center. At that time, Horwitz decided to seek a possible genetic reason after learning his patient had several family members with myelodysplastic syndrome, myeloid leukemia, and intractable mycobacteria infections.”
“Horwitz’s Australian colleagues had described a family with a similarly inherited blood disorder,” it added. “Eighteen years later, after rifling through many candidate genes, the researchers on both continents were relieved finally to have hit upon the mutated gene responsible for the leukemia that affect these families.”
They discovered the abnormal GATA2 genes in more than 20 patients and/or families, the researchers said, leading them to declare that the condition was “more common than we had though.”
The scientists are now trying to determine why gene mutations in GATA2 cause these types of health problems, and according to the press release, they believe that “additional knowledge about how the GATA2 gene and its mutations operate may foster the development of new therapeutic agents.”
The second study, which was led by researchers JoÃ£o T. Barata at Instituto de Medicina Molecular in Lisbon, Portugal and J. Andres Yunes at Centro Infantil Boldrini in Campinas, SÃ£o Paulo, Brazil, reported detecting mutations in T-cell acute lymphoblastic leukemia (T-ALL).
According to an Instituto de Medicina Molecular press release, the scientists discovered that these mutations allowed the cells to be eliminated through the use of “certain drugs, already in clinical use to treat other diseases.”
“The identification and study of mutations found in leukemia patients is particularly important to help develop more efficient and targeted therapies,” representatives from the institute said in that statement. “Researchers now found a group of mutations that affect 9% of the patients with T-ALL and that may originate leukemia in these patients“¦ Most importantly, researchers demonstrated that a set of pharmaceutical drugs can eliminate the effect of these mutations, unraveling a potential therapeutic application for their discovery.”
These mutations reportedly occur in the gene coding of the interleukin-7 receptor (IL7R), a protein located on the surface of T-cells. IL7R is used to transmit chemical information from the outside of the cell to the inside.
According to the press release, the researchers in this study discovered “that the mutations promote non-stop, uncontrolled T-cell proliferation, independently of extracellular triggers. This capacity to induce cells to grow relentlessly is associated with the ability to originate tumors.”
In order to combat these mutations, the scientists looked at drugs which are currently used to treat rheumatoid arthritis, and apparently can stop the cell proliferation in the mutated cells and wipe them out.
“We discovered that the interleukin-7 receptor, which is essential for proper T-cell development, may also have a ‘dark side’ “¦ In particular, we found that certain mutations in this gene are involved in pediatric T-cell acute lymphoblastic leukemia and characterized how they act,” Barata said in a statement.
“Our observations allowed us to identify potential therapeutic weapons against these tumors,” he added. “Although pediatric acute lymphoblastic leukemia is among the success stories in cancer therapy, improvements are still needed. We hope our findings will help further increase the efficacy and selectivity of already existing treatments.”
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