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Cancer, Red blood cells

25 years of LMO2: from bad guy to good guy

Twenty-five years ago the gene that codes for the protein LMO2 was discovered. To mark this anniversary, the lab that made this initial finding, now based in the WIMM, have written a review article to highlight the history, current understanding and continued importance of this remarkable protein in human health and disease. In this blog, Jennifer Chambers, a PhD student in the lab, focuses on some key characteristics of this complex protein.

The LMO2 gene was first found in children suffering from a form of leukaemia called T cell acute leukaemia, a form of blood cancer.

T cells are a type of cell which usually work in the immune system and help your body to fight infections. In the T cells of patients suffering from leukaemia, however, damage to the DNA causes LMO2 to be made and to work in T cells that do not normally have this protein.

Structure of the LM02 protein, showing in blue the site with which it interacts with other proteins to form a complex, and in brown ribbons the blocking molecule which inhibits its function.

Structure of the LM02 protein, showing in blue the site with which it interacts with other proteins to form a complex, and in brown ribbons the blocking molecule which inhibits its function.

But that’s not the whole story. LMO2 is also found almost half of all T-cell acute leukaemias that don’t have the characteristic DNA damage that doctors and scientists associate with the disease. And although LMO2 was previously only thought to cause cancer in T-cells, recent studies are linking LMO2 with other cancers such as pancreatic and breast cancer, as well as B-cell leukaemias (another type of immune cell in the blood).

Since LMO2 can cause cancer, developing therapies against LMO2 is more clinically significant than ever before. Research in our own and in other laboratories is underway to develop treatments based upon interfering with the way LMO2 works inside the cancer cell.

LMO2 acts as a glue in a protein complex that regulates how other proteins are made inside the cell. Without LMO2, this complex cannot form, and pre-clinical studies have shown that blocking the ability of LMO2 to form this complex is effective in stopping cancer growth in T cell leukaemias.

But LMO2 might not always be the bad guy. Rather than blocking LMO2 and inhibiting its function to prevent tumour growth, recent studies have now shown new properties of the protein that might make LMO2 itself useful as a therapy.

New research has shown that LMO2 is a key player in the process of making blood in the lab, by playing a role in converting “adult” blood cells back into blood stem cells. This could be of enormous benefit in personalised regenerative medicine where aging or dysfunctional blood cells could be replaced by new stem cells created from a patient.

With such a varied history since its first discovery, LMO2 has proved to be important in understanding many aspects of human health and disease, and has become a paradigm in investigating how DNA damage causes cancer. Research is continuing to find new facets to LMO2 biology and we hope that this will translate into better medicines for cancers and other diseases in the near future.

You can read the review article by the Rabbitts lab here.

Post edited by Bryony Graham and Terry Rabbitts.

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