Cambridge researchers have made a breakthrough in understanding a type of leukaemia in infants, which has baffled doctors for decades and limited improvements in treatment.
The research was led by scientists from the Wellcome Sanger Institute, Great Ormond Street Hospital and Newcastle University included Dr Sam Behjati, an honorary consultant at Cambridge University Hospitals (CUH) and a senior author of the study.
The team focused on a type of blood cancer called acute lymphoblastic leukaemia (ALL), a rare cancer most often diagnosed in children.
In particular they were looking at infant B-ALL cases, where cancer arises from a type of immune cell called B lymphocytes, more commonly known as B cells.
The study, published today in Nature Medicine, found subtle differences in the cell type that causes B acute lymphoblastic leukaemia (B-ALL) that may help to explain why some cases are more severe than others.
The findings provide a number of promising drug targets, raising hopes that effective treatments for infant B-ALL may be developed in the future.
This study offers compelling evidence that the maturity of the cells involved is a key factorDr Sam Behjati, honorary consultant CUH
Dr Sam Behjati, a senior author of the study from the Wellcome Sanger Institute, said:
“Though it is too early to draw definitive conclusions about why B acute lymphoblastic leukaemia (B-ALL) has much poorer outcomes in infants than in older children, this study offers compelling evidence that the maturity of the cells involved is a key factor.
"As well as generating new drug targets, these data will allow us to observe how the ‘cell type’ of certain cancers corresponds to patient outcomes, allowing us to better assess disease severity and determine the best course of treatment.”
More about acute lymphoblastic leukaemia (ALL)
Acute lymphoblastic leukaemia (ALL) starts from white blood cells called lymphocytes in the bone marrow, the soft inner part of the bones, where new blood cells are made.
ALL usually develops quickly over days or weeks and is the most common type of leukaemia to affect children, but can also affect adults.
Around 790 people are diagnosed with ALL in the UK each year.
B-ALL in children was once a universally fatal disease that is now curable in the majority of cases - except in children below the age of one.
For these very young patients, treatment is successful in less than 50 per cent of cases, with no significant improvement in the last two decades.
Treatments that are proven in tackling other forms of leukaemia, such as bone marrow transplants, have proved ineffective against infant B-ALL.
It is currently treated with strong chemotherapy, which can be hard for the patient to endure even if they are cured.
We think that we have unpicked why B-ALL is more responsive to treatment in some children, but why it’s not so successful for infants.Dr Jack Bartram, a senior author of the study, Great Ormond Street Hospital
Dr Jack Bartram, a senior author of the study from Great Ormond Street Hospital, said:
"Cancers with more ‘mature’ early lymphocyte precursors (ELPs) have characteristics that seem to respond better to treatment. These more mature cells are more common in B-ALL in older children but sadly not for our younger patients, meaning the treatment is less effective.
"The challenge now is to develop our understanding and confirm these suspicions so that we can improve treatments for all patients.”
In this paper, researchers set out to study KMT2A-rearranged infant B-ALL by comparing cancer cells to normal human blood cells.
Gene expression data from 1,665 childhood leukaemia cases was referenced against single-cell mRNA data from around 60,000 normal fetal bone marrow cells2.
Analysis found that infant B-ALL exhibited distinct cellular signals with a notable contribution from early lymphocyte precursors (ELPs)3, an immature immune cell type that normally develops into B cells.
Dr Laura Jardine, a first author of the study from Newcastle University, said:
“Leukaemias are usually classified by the cell type involved, and in the case of B acute lymphoblastic leukaemia (B-ALL) we talk about B cell progenitors. But our analysis of this disease has shown that this is actually an early lymphocyte precursor leukaemia”.
As well as being able to distinguish ELP cells from other types of B cell, the researchers found that the closer an ELP cell was to becoming a mature B cell, the better the outcome for the patient.
Click here to read the paper: https://doi.org/10.1038/s41591-022-01720-7
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