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MRC WIMM researchers have developed a new method to quickly identify cancerous cells in babies at risk of leukaemia. The team hope that the new protocol could make rapid testing more accessible for clinical laboratories around the globe.

3d rendered medically accurate illustration of the human blood cells and lymphocytes

Until now, the only reliable way to know if a baby with Down syndrome is at risk of developing leukaemia, an aggressive form of blood cancer, was by a relatively expensive DNA mutational analysis of a blood sample. Now, in a study published in Blood, the Vyas and Roberts groups at the MRC Molecular Haematology Unit (MHU) have developed an alternative, cheap method that quickly identifies cancerous cells. 

Babies with Down syndrome who have an alteration in the GATA1 gene have a remarkable propensity to develop a type of leukaemia known as ML-DS.30% of babies with Down syndrome have acquired mutations in the gene and 10% of them develop ML-DS before the age of 5. An altered GATA1 gene also it causes a pre-leukemic disorder known as TAM that in 20% of cases it is fatal. It is important to identify babies with the genetic mutation who are at risk of developing ML-DS or who suffer of TAM to provide the best care possible.

Ideally, babies born with Down syndrome are tested at birth for GATA1 mutations by next-generation sequencing methods. Unfortunately, not all hospital laboratories can make use of this relatively expensive method, especially developing countries, because it requires technical expertise and expensive equipment. In the hope of providing a solution to this problem, the Vyas and Roberts group have developed an alternative method. Instead of relying on DNA mutational analysis, their approach relies on flow cytometry, a method that is available in most haematology hospitals. The value of this simple method comes from quick and easy identification of GATA1 mutant cells in blood samples from new-born babies. The Vyas Group hope that one day most clinical laboratories around the world could make use of this method when next-generation sequencing methods are not available.

The GATA1 gene encodes two versions of a DNA binding protein important for healthy red blood cell and platelet production. These variants are known as GATA1fl and GATAs. Surprisingly, when mutations occur, they lead to exclusive expression of only GATA1s.

How GATA1s disrupts normal red blood cell and platelet production is still an unsolved problem. In another study published in Haematologica, the Vyas and Porcher laboratory developed a mouse cell platform to study where and how GATA1s disrupts blood formation. The team showed that, of the two blood lineages affected by exclusive GATA1s expression, the cell lineage responsible for platelet production is enhanced. The team noted that GATA1s cause immature blood cells, megakaryocytes, to accumulate and proliferate excessively. These cells mature aberrantly and show altered activity. This is incredibly important, as the malignant cells in TAM resemble immature proliferative megakaryocytes. This GATA1s driven megakaryocytic phenomenon could begin to explain the myeloproliferative disorder known as TAM. Eventually, the Vyas lab envisions this cellular platform could serve as a stage to test the molecular mechanism leading to TAM and ML-DS.

The Vyas, Porcher and Robert laboratories were funded by Bloodwise, the MRC Molecular Haematology Unit, NIHR Oxford Biomedical Centre Research Fund and Lady Tata Memorial Trust.

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