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Role of CCN3 Hypermethylation in CML

By: Joseph Fanelli
Posted: Wednesday, May 15, 2019

According to findings presented in Cell Communication and Signaling, the nephroblastoma overexpressed (NOV) gene product CCN3 hypermethylation may act as a molecular mechanism independent of BCR-ABL1 function in patients with chronic myeloid leukemia (CML). The possible revelations about CCN3 hypermethylation suggest that the gene may serve as an early trigger for CML formation, concluded Mahmood Tavallaie, PhD, of the Human Genetics Research Center at the Baqiyatallah University of Medical Sciences, Tehran, Iran, and colleagues.

“Having clonogenic activities and being involved in several properties of hematopoietic stem cells, we assume the CCN3 hypermethylation as a candidate initiator of CML, which can provide the clonal domination of BCR-ABL–positive cells,” the authors observed. “However, further studies are required to clarify the exact influence of NOV DNA hypermethylation by analyzing a comprehensive set of signaling pathways involved in the disease.”

The researchers applied a bisulfite-sequencing technique as a high-resolution method to observe the regulatory segment of the CCN3 gene in 20 patients who were recently diagnosed with CML and received imatinib therapy. Of the cohort, nine patients were classified as having chronic phase CML, five were in accelerated phase, and six were in blastic phase. The correlation between the CCN3 promoter methylation and BCR-ABL1 levels was also evaluated.

Methylation seemed to occur frequently in the promoter region of patients with CML who showed a significant increase in the methylated percentage at the CpG sites, compared with individuals without CML. The authors noted that the presence of hypermethylation was independent of BCR-ABL1 titers in both groups, suggesting a possible mechanism beyond BCR-ABL1 function. Even patients with suboptimal molecular responses or no molecular response displayed NOV hypermethylation, whereas no significant changes were observed in the level of NOV hypermethylation in various clinical staging with the treatment responses.

Disclosure: The study authors reported no conflicts of interest.



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