Adult T-Cell Leukemia: a Comprehensive Overview on Current and Promising Treatment Modalities

Abstract

Purpose of the ReviewAdult T-cell leukemia (ATL) is an aggressive chemo-resistant malignancy secondary to HTLV-1 retrovirus. Prognosis of ATL remains dismal. Herein, we emphasized on the current ATL treatment modalities and their drawbacks, and opened up on promising targeted therapies with special focus on the HTLV-1 regulatory proteins Tax and HBZ. Recent Findings Indolent ATL and a fraction of acute ATL exhibit long-term survival following antiviral treatment with zidovudine and interferon-alpha. Monoclonal antibodies such as mogamulizumab improved response rates, but with little effect on survival. Allogeneic hematopoietic cell transplantation results in long-term survival in one third of transplanted patients, alas only few patients are transplanted. Salvage therapy with lenalidomide in relapsed/refractory patients leads to prolonged survival in some of them. Summary ATL remains an unmet medical need. Targeted therapies focusing on the HTLV-1 viral replication and/or viral regulatory proteins, as well as on the host antiviral immunity, represent a promising approach for the treatment of ATL.

Primary cells from patients with adult T cell leukemia/lymphoma depend on HTLV-1 Tax expression for NF-κB activation and survival

“…In conclusion, our results pinpoint that ATL is not only a virus-initiated leukemia, but also a virus-addicted malignancy, providing a strong rationale for the clinical development of Tax- targeting therapy [ 64 ]. Potential candidates include IFN and ATO which induce Tax degradation by the proteasome [ 17 , 37 – 42 ], anti-Tax immunotherapy [ 33 ] including therapeutic vaccines [ 36 ], allogeneic stem cell transplantation through Tax-specific CTL [ 65 ], or chimeric antigen receptor (CAT) T or natural killer cells.…”

The Roles of FHL3 in Cancer

“…Adult T-cell leukemia (ATL) is an aggressive drug-resistant hematological malignancy tumor secondary to HTLV-1 retrovirus infection ( 37 ). The prevalence of HTLV-1 is mainly attributed to vertical transmission via breast feeding.…”

Prediction of the Adult T-Cell Leukemia Inhibitory Activity of Blueberry Leaves/Stems Using Direct-Injection Electron Ionization-Mass Spectrometry Metabolomics

“…In addition, we reported that V. virgatum leaves prevent the proliferation of adult T-cell leukemia (ATL) cells [ 12 , 13 ]. ATL is an aggressive chemotherapy-resistant malignancy secondary to infection with the retrovirus human T-cell leukemia virus type 1 (HTLV-1) [ 14 ]. Based on these studies, agricultural efforts have focused on breeding V. virgatum leaves for use as green tea, although the leaves have not previously been used as a food ingredient.…”