Mystery of treatment-resistant childhood leukaemia uncovered, a new subtype of cancerous T-cells is identified

Good news! Cancer is history (soon)!

"A team ... and their collaborators mapped the origins of T-cell leukaemia. They identified a new subtype of cancerous T-cells that does not respond to current treatments and could be responsible for the high mortality in this type of childhood cancer.

The research ... pinpointed the gene that is switched on in these cells, and how to identify them. These cells could be identified by adapting tests that are already used routinely by clinicians and could therefore be easily integrated into clinical care.

Being able to identify children whose cancer will not respond to treatment could directly impact their clinical care. For example, allowing them to avoid chemotherapies that have been proven to be ineffective against resistant cancers and prioritise other treatments.

Acute lymphoblastic leukaemia (ALL) affects the blood and bone marrow and is the most common type of childhood cancer, with 400 children diagnosed in the UK each year. There are two different groups depending on which immune cells are affected: B-cell leukaemia (B-ALL) and T-cell leukaemia (T-ALL).

In general, outcomes for B-ALL have improved over the past few decades due to the development of new immunotherapies and the identification of genomic subgroups that can help tailor treatment.

However, T-ALL makes up around 15 per cent of total cases and is a more aggressive disease. It has higher rates of treatment failure and drug resistance, which occur in about 10 percent of children with T-ALL4. ..."

From the abstract:

"Refractory cancers may arise either through the acquisition of resistance mechanisms or represent distinct disease states.
The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown.
Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we perform single cell mRNA sequencing of T-ALL from 58 children (84 samples) who did, or did not respond to initial treatment.

We identify a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease.
Evidence of such blasts at diagnosis heralds refractory disease across independent datasets and is associated with survival in a large, contemporary trial cohort.
Our findings portray refractory T-ALL as a distinct disease with the potential for immediate clinical utility."

Mystery of treatment-resistant childhood leukaemia uncovered "A new type of cancer cell that “warrants urgent investigation” has been discovered in childhood leukaemia and could impact clinical care. Research into new or repurposed treatments that target this new cell type could give hope to children and families worldwide. "

A non-canonical lymphoblast in refractory childhood T-cell leukaemia (open access)

Fig. 1 ZBTB16 defines refractory blasts in T-ALL