Mechanisms of in utero damage to fetus

01 February 2012
Dr Patrick Case, University of Bristol

The first stage in the development of childhood leukaemia occurs before birth in at least some cases. The human placenta acts as a protective barrier, preventing harmful toxins crossing from the mother’s blood into the developing fetus. Dr Case has uncovered a mechanism by which certain toxins transmit damage across the placenta and is taking forward this work to discover whether this could be a factor in the early development of childhood leukaemia.  

Amount of award: £99,844  │ Date of award: February 2012


Leukaemia is the most common form of childhood cancer, affecting up to 500 children every year in the UK. The development of childhood leukaemia is thought to occur in two stages with the first stage occurring before birth in at least some cases.

Dr Case and colleagues have discovered a new mechanism which could explain how a baby might be damaged during pregnancy, and they are now testing whether this could explain the first stage of childhood leukaemia.

In human pregnancy, there is barrier in the placenta separating the blood of the baby and the mother. The team has found that chemicals, toxic particles or altered oxygen cause laboratory models of this barrier to secrete substances that damage the DNA of human cells on the other side (i.e. potentially on the baby’s side).

In this project, they are now testing whether these signals from human placenta can cause DNA damage and chromosome aberrations in human fetal blood cells and whether this damage is similar to that observed in childhood leukaemia. They will test at which stage of development the blood cells might be damaged and whether damage leads to altered cellular function of the kind that is associated with leukaemia. They will also test whether altering a naturally protective mechanism in cells (autophagy) could influence this process, thereby exploring a new therapeutic concept.

About the research team

Dr Patrick Case is a Consultant Senior Lecturer in Orthopaedics with Pathology at the University of Bristol and Southmead Hospital. His previous work on the genotoxicity of orthopaedic implants has led to new advice for surgeons, manufacturers and patients (including during pregnancy).

Dr Case is jointly supervising the project with Dr Jon Lane, of the University of Bristol School of Biochemistry, and Dr Allison Blair, of NHS Blood and Transplant, both of whom bring complementary expertise to the project.

What difference will this project make?

This ground-breaking work will take forward our understanding of the mechanisms by which environmental toxins could harm the developing fetus and whether this could be a factor in the causation of childhood leukaemia.

The team is also testing a new concept in therapy which could lead to a new treatment approach for childhood leukaemia.

Read more: About acute lymphoblastic leukaemia | Acute myeloid leukaemia | Causes of childhood cancer

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