Leta i den här bloggen


onsdag 3 oktober 2018

T-soluleukemia, perifeerinen T-solumaligniteetti, T-lymfotrooppivirus. Uutta terapiastrategiaa

https://www.ncbi.nlm.nih.gov/pubmed/28978842
Rinsho Ketsueki. 2017;58(10):2004-2011. doi: 10.11406/rinketsu.58.2004.

Molecular pathogenesis and its therapeutic implication for ATL.

[Article in Japanese]
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1).

 HTLV-1 related proteins Tax and HTLV-1 bZIP factor induce immortalization and transformation of HTLV-1-infected T-lymphocytes and eventually induce clonal proliferation.

One of the apparent molecular features in ATL cells is abundant genomic abnormalities targeting characteristic pathways, including T-cell receptor signaling and the NF-κB pathway,
 G-protein coupled-receptor, including CCR4, and transcriptional regulation.

 Moreover, the overexpression of PD-L1 caused by structural variations in the 3'-UTR of the PD-L1 gene has been reported recently, which indicates possible escape of ATL cells from immune-surveillance and its therapeutic application for pharmacological intervention.

 The next is the downregulation of microRNAs and tumor suppressors by genome-wide epigenetic abnormalities, especially accumulation of trimethylated H3K27 induced by EZH2.

 Among these molecular events frequently observed in ATL cells, treatment targeting CCR4 via a monoclonal antibody (Mab)  has been introduced in the clinic, and immune-therapy by therapeutic vaccine with Tax peptide-pulsed dendritic cells, treatment by immune checkpoint inhibitors (ICI) , and treatment targeting EZH1/2 by a small molecule inhibitor are under clinical trial.

 Establishment of novel treatment strategies beyond cytotoxic agents for ATL are eagerly anticipated, especially for elderly patients.

KEYWORDS:

ATL; Molecular pathogenesis; Novel therapy
PMID:
28978842
DOI:
10.11406/rinketsu.58.2004
[Indexed for MEDLINE]

Inga kommentarer:

Skicka en kommentar