The lymphoid tumor known as adult T-cell leukemia (ATL) is brought on by human T-cell leukemia virus type 1 (HTLV-1), which produces the transcriptional activator Tax that aids in the immortalization of infected T cells. ATL is divided into 4 subtypes: lymphoma, smoldering, chronic, and acute. For a study, researchers looked at the expression of natural killer receptors (NKRs) in ATL.

In a discovery cohort of 21 ATL, NKR expression (KIR2DL1/2DS1, KIR2DL2/2DL3/2DS2, KIR3DL2, NKG2A, NKG2C, and NKp46) was evaluated. KIR3DL2 was then evaluated in 71 individuals with ATL. Despite having comparable mutation patterns by targeted exome sequencing, KIR3DL2 was the only NKR examined that was often expressed by acute-type vs. lymphoma- and chronic/smoldering-type ATL (36 of 40, 4 of 16, and 1 of 15, respectively; P=.001). Microarray-based DNA methylation profiling was used to examine the relationship between KIR3DL2 expression and promoter demethylation. KIR3DL2 and TAX messenger RNA (mRNA) expression levels were measured by PrimeFlow RNA in primary ATL and in CD4+ T cells infected with HTLV-1 in vitro to investigate the role of HTLV-1.

On ATL cells, there was a correlation between the expression of TAX mRNA and KIR3DL2. CD4+ cells expressed KIR3DL2 in response to HTLV-1 infection, although Tax alone did not cause this expression. Lacutamab, a first-in-class anti-KIR3DL2 humanized antibody, was used to kill KIR3DL2+primary ATL cells ex vivo by autologous, antibody-dependent cell cytotoxicity.

In conclusion, acute-type ATL is related to KIR3DL2 expression. Hypomethylation of the promoter is correlated with the transcription of KIR3DL2, which may be induced by HTLV-1 infection. In a randomized phase 2 research, KIR3DL2 targeting with lacutamab was being investigated further in peripheral T-cell lymphomas, including ATL.

 

Reference: ashpublications.org/blood/article-abstract/140/13/1522/485527/KIR3DL2-contributes-to-the-typing-of-acute-adult-T?redirectedFrom=fulltext