The Institute of Cancer Research experts analysed the entire three billion letter sequence of DNA-coding in identical twins to reveal what sets off the disease.
They hope the findings, published in PNAS journal, could lead to new drugs to fight the condition at source.
Leukaemia is the most common cancer diagnosed in children.
It affects a third of young cancer sufferers and kills 100 children a year in the UK.
The twins studied by the researchers had the most common form of leukaemia that affects children – acute lymphoblastic leukaemia (ALL) which is a cancer of the white blood cells.
It is already known that multiple faulty genes are linked to the condition and that environmental factors probably act as triggers along the way. But the precise sequence of events leading up to a diagnosis of ALL is unclear.
The researchers wanted to find out more about the disease so that, ultimately, a better treatment could be found.
Although ALL is often curable, the medicines used to treat it can cause unpleasant and sometimes severe side effects.
Prof Mel Greaves and his colleagues decided to study identical twins who shared the same DNA inherited from their parents.
Both twins developed ALL in early childhood, at around four years of age.
By comparing blood and bone marrow samples of the twins in later childhood, the researchers found one genetic mutation identical in both twins – a common leukaemia-causing gene called ETV6-RUNX1.
The researchers reason that this mutation must have arisen in one of the twins while in the womb.
Cells carrying the mutation then spread to the other twin via their shared placental blood circulation.
The identical twins had a total of 22 other mutations, but none of these mutations was shared by both twins, and so they must have accumulated after birth as the disease progressed, say the researchers.
Study co-author Prof Greaves said: “We were able to sequence the entire human genome. It told us for the first time that this is the key mutation that starts the whole process of leukaemia. The other mutations must have happened after birth.”
Dr Julie Sharp of Cancer Research UK said: “This interesting research shows how studying the DNA of twins can shed light on the genetic mistakes that first initiate cancer in children and the subsequent faults that occur as the cancer evolves.
“Studies like this could reveal new ways to target the very roots of cancer and help us better understand how the disease develops over time. Survival rates have increased significantly over the past decades thanks to research, but there is still more to do to make treatments better with fewer side-effects.”
Source : BBC