Barcelona develops six-gene score to predict survival in AML — News-Medical
Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have developed a score based on the activity of six genes that could improve predictions of survival for patients with acute myeloid leukemia (AML). The results were published in the journal Science Advances, News-Medical reports.
Six genes for prognosis assessment
The scientists developed the PHFScore system by comparing the results of experiments in mice with patient data. They identified six genes whose activity was associated with different survival rates. Patients with less favorable outcomes had higher activity of the CARMIL1, HOPX and ALDH1A1 genes, while the activity of CALR, STAR and PHF19 was lower.
The combined analysis of these six genes divided patients into groups with significantly different survival prospects. According to the study's senior author, ICREA Professor Luciano Di Croce, the PHF19 gene alone already provides information for prognosis, but combining it with the other five genes makes the assessment more accurate.
Results from experiments and patient data
The team initially focused on PHF19, a gene belonging to a family of genes that suppress the activity of other genes during cell maturation. In previous studies by Di Croce's laboratory, mice without PHF19 had a condition similar to myelodysplastic syndrome: blood cells did not mature properly and accumulated in the body.
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In the new study, the scientists introduced a leukemia-causing gene into blood cells of mice with and without PHF19. Cells without PHF19 formed more colonies under laboratory conditions, engrafted more easily after transplantation into mice, and remained in an immature, stem cell-like state. These cells also largely did not respond to chemotherapy drugs used to stimulate the maturation of leukemia cells.
When compared with human data, a similar molecular pattern was also found in patients. Among younger adults treated for AML, patients with the lowest PHF19 levels lived for a shorter time and achieved remission less often after standard chemotherapy: remission occurred in fewer than half of them, while among patients with the highest PHF19 levels, this figure reached up to 85%.
The authors believe that PHFScore could become the basis for future prognostic tests. A bone marrow sample is already taken from patients suspected of having AML, and measuring the activity of six genes may be simpler and cheaper than broader genetic profiling.
