Scientists Map Link Between Virus and Rare Type of Leukaemia

Peter Russell

December 16, 2021

Scientists say they have discovered new clues for how Human T-lymphotropic virus type 1 (HTLV-1) causes a rare type of leukaemia.

The team, led by Imperial College London and Kumamoto University in Japan, say the findings could aid further research into the molecular mechanism underlying HTLV-1 infection and adult T cell leukaemia/lymphoma (ATL).

Although it is known that HTLV-1 alters cellular differentiation, activation, and survival, it has not been understood whether – and how – these changes contribute to the malignant transformation of infected cells.

The study, published in The Journal of Clinical Investigation , found that HTLV-1 can insert itself into one type of T cell where it can hide from the immune system.

The virus initially remains in a latent state, but in around 5% of carriers, the infected cells transform into leukaemic cells, often decades later, according to the researchers.

Virus Can Lead to Over-reactive T Cells

To reach its conclusions, the team analysed 87,742 T cells from virus-free donors, healthy carriers of HTLV-1, and patients with ATL.

The results suggest that in individuals with ATL, HTLV-1 made infected T cells highly activated, causing them to over-produce proteins that keep them proliferating and helping them avoid the immune system.

The changes could make the over-reactive T cells more vulnerable to DNA damage, accelerating transition to a cancerous state, the researchers believe.

Masahiro Ono, an immunologist and specialist in T cell regulation from Imperial College London, and study co-author, said it was important to understand "how the virus turns our T-cells against us" as a precursor to cancer. "Our work highlights a key mechanism for this change and provides us with new directions to search for ways to interfere with the process, potentially preventing the cancer from developing," he said.

Prof Yorifumi Satou, a Japanese virologist studying HTLV-1, and study co-author, said: "While only a small percentage of people with HTLV-1 viral infections go on to develop adult T cell leukaemia/lymphoma, there are estimated to be around 50 to 10 million carriers of the virus worldwide, and in some areas it is endemic. For example, there are around 1 million cases in Japan."

Cases are also very common in the Caribbean basin, Central and South America, Iran, Romania, and parts of Africa.

In the UK, ATL is very rare, with around 30 people diagnosed each year.

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