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Scientists discover Y chromosome gene can protect against leukaemia

It is hoped the findings could lead to new treatments for acute myeloid leukaemia, which has poor long-term survival rates.

Scientists have discovered a gene specific to the male-only Y chromosome protects against the development of acute myeloid leukaemia (AML) and other cancers.

AML is an aggressive blood cancer that affects people of all ages. It develops in cells in the bone marrow and leads to life-threatening infections and bleeding.

Mainstream treatments for the condition have remained unchanged for decades and just 20% of patients survive for five years or more after diagnosis.

Researchers at the Wellcome Sanger Institute and the University of Cambridge said the discovery of this new role changes the way the Y chromosome is viewed and improves understanding of how AML and other cancers develop.

Health experts said their findings could lead to new lines of research for new treatments for AML, which has poor long-term survival rates. Around 2,600 people are diagnosed with it every year in the UK.

Women have two X chromosomes whereas men have one X and one Y chromosome. The X and Y chromosomes share many genes, but a small number of genes, including UTY, are only found on the Y chromosome.

These Y-specific genes were thought to contain the genetic information required for male sexual characteristics, but were not known to have other roles.

Our study strengthens the argument that loss of the Y chromosome can increase the risk of cancer Professor Brian Huntly

The team studied the X-chromosome gene UTX in human cells and in mice to try to understand its role in AML.

They found the loss of the X-chromosome gene UTX, which is known to be mutated in many tumours, hastens the development of AML.

However, they found that UTY, a related gene on the Y chromosome, protected male mice which were lacking UTX from developing AML.

The study, published in Nature Genetics, showed that in AML and in several other human cancers types, loss of UTX is accompanied by loss of UTY, meaning the cancer-suppressing role of UTY extends beyond AML.

Lead author Dr Malgorzata Gozdecka, of the Wellcome Sanger Institute, said: “Previously it had been suggested that the only function of the Y chromosome is in creating male sexual characteristics, but our results indicate that the Y chromosome could also protect against AML and other cancers.”

Professor Brian Huntly, of the University of Cambridge and a consultant haematologist at Cambridge University Hospitals NHS Trust, said: “It is known that men often lose the Y chromosome from their cells as they age, however the significance of this was unclear.

“Our study strengthens the argument that loss of the Y chromosome can increase the risk of cancer and describes a mechanism for how this may happen.”

Dr Alasdair Rankin, director of research at the charity Bloodwise, said: “Survival rates for AML remain tragically low, with current treatment that involves intensive chemotherapy, often combined with a stem cell transplant, only curing a small proportion of patients.

“This important research helps build a fuller picture of what goes wrong genetically as this highly aggressive leukaemia develops. Understanding this process is key to developing targeted drugs for AML, allowing us to move away from gruelling and often ineffective chemotherapy-based treatments.”

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