Scientists from Hokkaido University have found a new target physicians could use when treating patients with severe leukaemia. T-cell leukaemia/lymphoma in adults is a serious blood cancer which scientists have correlated with a virus.
There is no effective treatment for ATLL
Unfortunately, the survival rating for this disease is 20%. To add to this, available chemotherapy drugs don’t work effectively in treating it. Scientists have had difficulty finding therapies for ATLL since there is no single pathway or gene mutation in patients with the disease. Each patient is affected differently.
The scientists used gene editing to inactivate several genes in ATLL cell lines. They did this to identify pathways that scientists could target when developing a treatment for the disease. From their study, they found 1278 genes that ATLL cells need to survive and proliferate. Afterwards, they reduced them to nine genes to investigate them.
Researchers assessed the CDK6 and TP53 genes
CDK6 was one of the nine genes. The team found that this could be one of the best chemotherapy targets. When they used palbociclib, a breast cancer drug, to inactivate the enzyme, the ATLL cells stopped divided. They also reported cell death in some of the cells.
The team also identified a mutation in TP53, another gene, which was responsible for causing drug resistance. This gene typically works by preventing tumour growth in the body. Fortunately, the therapy worked when the researchers used a combination of palbociclib and a drug that could activate the mutated TP53. Physicians typically use the latter to treat the myelodysplastic syndrome.
The team also tried to treat ATLL cells with everolimus, which treats breast and kidney cancer. This drug managed to treat ATLL cells and mutations to the TP53 gene. The drug worked by inhibiting mTORC1, which played a role in cell proliferation and growth.
According to one of the study authors, Dr Nakagawa, the researchers noted CKD6 was the best target for treating the disease. He adds that the TP53 mutations were also a significant aspect of the disease. These mutations caused resistance to palbociclib. This finding was essential in determining treatment for patients with ATLL.