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Birmingham [UK], June 22 : A discovery that may result in novel medicines to halt or reverse the disease could be beneficial to patients with a rare genetic bone marrow problem who are at an elevated risk of blood malignancies.Researchers from the Universities of Birmingham and Warwick have discovered that damaged blood stem cells formed in bone marrow produce significantly less immune cells needed to fight infection in a recent study published in Cell Reports. These blood stem cells' decreased capacity to repair continuing DNA damage puts patients at risk for developing blood malignancies. This is due to a mutation in the GATA2 gene. The average patient with this disease who develops acute myeloid leukaemia is 20 years old.Dr Rui Monteiro, Associate Professor in the Institute of Cancer and Genomic Sciences at the University of Birmingham and lead author of the paper said:"GATA2 deficiency is a rare disorder, where the bone marrow fails to produce sufficient immune cells due to pathogenic mutations in the GATA2 gene."Our lab has a developed a zebrafish model of the GATA2 deficiency and we have used genomics to discover how blood stem cells affected by the mutations in the GATA2 gene produce far fewer immune cells, particularly granulocytes and macrophages. Besides blunting of the immune system, the ability to deal with DNA damage in blood stem cells is impaired, which increases the likelihood of cells acquiring further mutations that lead to blood cancers."This work has thus uncovered a potential mechanism for disease progression in the human patients and will enable further investigation on ways to block, slow down or revert the appearance of blood cancers in GATA2 deficiency patients."Patients who have GATA2 deficiency can present at clinics with a wide range of symptoms including recurrent viral or bacterial infections, and the new study has identified the reason why these specific immune cells are being produced in much smaller numbers in patients.The Monteiro lab based at the University of Birmingham developed a zebrafish model of this disease and used single cell genomics approach to better understand how disease progression occurs in these patients.Blood stem cells affected by mutations in the GATA2 gene were found to produce much less granulocytes and macrophages and are therefore less able to fight off infections. They are also less able to repair damage to their DNA, which leads to increased genome instability and higher likelihood of acquiring further mutations that in turn lead to the occurrence of blood cancers at a younger age.Disclaimer: This post has been auto-published from an agency feed without any modifications to the text and has not been reviewed by an editor

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Institute of cancer and genomic sciences, Latest News

Technology :Genetic mutations direct immune defences in leukaemia linked rare bone marrow disorder: Study

Birmingham [UK], June 22 : A discovery that may result in novel medicines to halt or reverse the disease ... ...