Research Highlight

Potential prognostic marker for chronic lymphocytic leukemia

doi:10.1038/nindia.2017.78 Published online 10 July 2017

Scientists have identified a novel marker that could help predict the progression of chronic lymphocytic leukemia (CLL)1.

CLL occurs when a genetic mutation causes B-cells, responsible for creating white blood cells, to grow uncontrollably. Eventually, these abnormal cells accumulate in the blood and other organs, crowd out healthy cells, and interfere with healthy blood cell production.

Despite several known markers — gene expression, genetic aberrations, and perhaps most tellingly, immunoglobulin heavy chain gene mutation status — to assess patients’ risk, the prognosis of CLL is highly variable.

Researchers led by Ritu Gupta of the All India Institute of Medical Sciences in New Delhi pooled samples from a small cohort of CLL patients to identify differentially methylated genes. By integrating these data with gene expression profiles, the researchers found that patients without mutated immunoglobulin heavy chain showed significant hypomethylation of PAX9—an epigenetic change in a region that affects the expression of other proteins.

Next, the group demonstrated that mRNA expression levels of PAX9 and CRY1, a gene for which methylation status and expression levels have previously been associated with CLL prognosis, were significantly elevated in patients without mutated immunoglobulin heavy chain. This subgroup was more likely to need treatment, and more likely to need treatment sooner. High expression of PAX9 was also predictive of shorter overall survival.

Notably, PAX9 and CRY1 expression levels did not vary across CLL and control groups, but between CLL patients sub-grouped by immunoglobulin heavy chain mutational status. “It is plausible that these two genes may be involved in the progression of CLL rather than the development of the disease,” the authors write.


1. Rani L. et al. Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia. Clin. Epigenetics. 9, 57 (2017)