Evaluation of ALKBH2 gene expression in patients with adult T-cell leukemia

Abstract

Background Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic virus that causes adult T-cell leukemia (ATL). Patients infected with HTLV-1 are considered HTLV-1 carriers, and a small proportion of patients progress to life-threatening ATL after a long asymptomatic phase. Although countermeasures have been developed to combat HTLV-1 infection and ATL, their pathogenesis remains unclear. Recently, members of the AlkB homolog (ALKBH) family have been shown to participate in oncogenesis in various cancer types, and ALKBH2 is intensively investigated as an interesting candidate in the research field of cancer. To investigate the potential role of ALKBH2 in the pathogenesis of ATL, we analyzed their gene expression dynamics in peripheral blood mononuclear cell-derived clinical specimens obtained from asymptomatic HTLV-1 carriers and patients with acute-type ATL. Results The mRNA expression level of ALKBH2 was significantly decreased in asymptomatic HTLV-1 carriers, but reverted in patients with acute-type ATL, correlating with HTLV-1 basic leucine zipper (HBZ) gene expression. Analysis of HBZ transgenic mice suggested inhibited trend of ALKBH2 pre-mRNA expression, and unbalanced mRNA and pre-mRNA expression of ALKBH2 in spleen cells. Then, the pre-mRNA expression of ALKBH2 was investigated in clinical specimens, and it was revealed that they were significantly suppressed in patients infected with HTLV-1, but not in healthy controls. It was also confirmed the unbalanced mRNA and pre-mRNA expression of ALKBH2 was prominent in patients with acute-type ATL. Conclusions We discovered dynamically regulated patterns of ALKBH2 gene expression in patients infected with HTLV-1. This study provides novel insights into the roles of ALKBH2 and HBZ in HTLV-1 infection, and contributes to understanding the pathogenesis of ATL.