Human T-cell lymphotropic virus HBZ and tax mRNA expression are associated with specific clinicopathological features in adult T-cell leukemia/lymphoma


Mod Pathol. 2020 Sep 24. doi: 10.1038/s41379-020-00654-0. Online ahead of print.


Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell leukemia virus type 1 (HTLV-1). HTLV-1-associated mRNA, including HBZ and tax, is deeply involved in the pathogenesis of ATLL. Using 88 ATLL tissue samples, we performed in situ mRNA analysis of HBZ and tax, and investigated its association with clinicopathological characteristics of ATLL. The median value of HBZ signals (/1000 ATLL cells) was 795.2 (range: 0.4-4013.1) and of tax signals (/1000 ATLL cells) was 5.1 (range:

0.1-891.2). The low-expression HBZ group displayed significant increase in the number of skin lesion (P = 0.0283). The high-expression tax group displayed significant increase in the number of PD-1-positive tumor-infiltrating lymphocytes (P < 0.0001). In addition, we identified patients with very high-expression of tax signals (400 or more signals/1000 ATLL cells). These patients displayed significant reductions in the expression of HLA class I (P = 0.0385) and β2M (P = 0.0124). Moreover, these patients displayed significantly poor overall survival (median survival time [MST] 7.7 months, 95% confidence interval [CI] [4.7-NA]), compared with the survival in patients with less than 400 tax signals (MST 22.6 months, 95% CI [13.7-41.7]) (P = 0.0499). These results suggest that Tax-mediated treatment of ATLL should be performed carefully in the high-expression tax group. More detailed studies could elucidate the clinicopathological significance of HBZ and tax mRNA expressions in ATLL.