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Review
. 2018 May 9:9:925.
doi: 10.3389/fmicb.2018.00925. eCollection 2018.

Future Perspectives on Drug Targeting in Adult T Cell Leukemia-Lymphoma

Francesca Marino-Merlo  1 , Antonio Mastino  2   3 , Sandro Grelli  4 , Olivier Hermine  5 , Ali Bazarbachi  6   7 , Beatrice Macchi  1
Affiliations
Review

Future Perspectives on Drug Targeting in Adult T Cell Leukemia-Lymphoma

Francesca Marino-Merlo et al. Front Microbiol. .

Abstract

Human T cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia/lymphoma (ATL), HTLV-1 associated myelopathy (HAM/TSP), and of a number of inflammatory diseases with an estimated 10-20 million infected individuals worldwide. Despite a number of therapeutic approaches, a cure for ATL is still in its infancy. Conventional chemotherapy has short-term efficacy, particularly in the acute subtype. Allogeneic stem cell transplantation offers long-term disease control to around one third of transplanted patients, but few can reach to transplant. This prompted, over the past recent years, the conduction of a number of clinical trials using novel treatments. Meanwhile, new data have been accumulated on biological and molecular bases of HTLV-1 transforming and infecting activity. These data offer new rational for targeted therapies of ATL. Taking into account the double-face of ATL as an hematologic malignancy as well as a viral infectious disease, this Mini-Review seeks to provide an up-to-date overview of recent efforts in the understanding of the mechanisms involved in already used therapeutic regimens showing promising results, and in selecting novel drug targets for ATL.

Keywords: ATL; HTLV-1; antiviral agents; biological therapy; targeted therapy.

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Figures

FIGURE 1
FIGURE 1
HTLV-1 driven leukomogenesis and possible mechanism of antiviral therapy. (A) Main immortalization/transformation process activated by HTLV-1 regulatory protein Tax and HBZ in newly infected CD4+ cells transmit virus to uninfected CD4+ cells and leading to epigenetic and genetic changes in ATL transformed cells. Cell migration and cell-to-cell virus transmission, presumably involving also dendritic cells, favor the release of inflammatory cytokines and chemokines milieu in the microenvironment and contribute to the maintaining of the infected clones. (B) AZT/IFN with or without arsenic trioxide (AS) could interrupt the maintaining route of ATL.
FIGURE 2
FIGURE 2
Novel approaches for ATL therapy. (A) Biological therapy with monoclonal antibodies and corresponding targets involved in neoplastic signaling in ATL cells. (B) Compounds and corresponding targets potentially useful for innovative targeted therapies in ATL.
See this image and copyright information in PMC

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