A new study has found that if the HLF (hepatic leukaemia factor) gene that is expressed in immature blood cells does not shut down on time, then it is unable to develop a functional long-term immune system and this could be a very early stage of leukaemia.
Blood stem cells give rise to all of our blood cells: the red blood cells that transport oxygen, the platelets that enable blood coagulation, and our immune cells that protect us from infections.
Immune cells divided into two groups. One that consists of cells with a very short life expectancy and ability to counteract infections (myeloid cells), and another that consists of very long-lived cells (lymphocytes) that specialize in combatting specific bacteria and viruses.
The ability of blood stem cells to form all types of blood cells is a fundamental property that is also utilized in connection with bone marrow transplants. An increased understanding of the processes is crucial.
Immune cells in patients who undergo bone marrow transplants are regenerated very slowly, which results in a long period of immune sensitivity, said David Bryder who was in charge of the study.
Despite the fact that all of our genes have been mapped, it is still largely unknown how the genes are controlled. What a cell can and cannot do is governed entirely by how the cell uses its genome.
The team have searched for genes expressed in immature blood cells but which disappear in connection with their further maturation. Then the researchers discovered the HLF gene, which controls what parts of our DNA are to be used, and is directly involved in a rare but very aggressive type of blood cancer.
The study findings revealed that if the immature blood cells are unable to shut down the HLF gene at the correct stage of development, the lymphocytes — the long-lived immune cells — are unable to form. As a result, the body will only have one type of immune defence.
A single cell must undergo a variety of changes to become cancerous. However, the earliest changes may involve the HLF gene, which gives rise to a precursor to leukaemia. Patients with leukaemia in which the HLF gene is involved have a very poor prognosis.
However, it has been difficult to generate reliable models for studying the emergence, development and possible treatment of these leukaemias more thoroughly. The team aimed to identify the mechanisms that can be used to break down these aggressive leukaemias.
David Bryder concluded, "The knowledge and experimental model systems we developed concerning how HLF affects blood cell development enables us to map the order of gene mutations that lead to HLF-generated leukaemia, which is an important next step towards our goal."