Imbalanced expression of α and β isoforms of PRDM1 contributes to the pathogenesis of nasal type NK/T-cell lymphoma

Abstract

One of the main characteristics of nasal NK/T-cell lymphoma (NKTCL) is frequent deletions on chromosome 6q. PRDM1 is a tumour suppressor gene located in 6q21, and its protein exists as two isoforms (α and β), generated from the same locus via alternative transcription initiation sites. PRDM1α isoform was previously shown to have tumor suppressive effects in NKTCL. As PRDM1β lacks a positive regulatory (PR) domain but maintains normal DNA-binding activity, it was proposed as a negative regulator of PRDM1α, though its role in the pathogenesis of NKTCL has not been elucidated. Our study showed that upregulation of PRDM1β via tumor-specific promoter hypomethylation counteracted the tumor suppressive effects of PRDM1α. In addition, NKTCL patients (n=17) showing both PRDM1α promoter hyperemethylation and PRDM1β promoter hypomethylation had inferior overall survival (p=0.046) compared to patients with PRDM1α promoter hypermethylation alone, when treated with the SMILE regimen. In conclusion, the imbalanced expression of the α and β isoforms of PRDM1 contributes to the pathogenesis of NKTCL and influences prognosis of these patients.