Hlf gene modulates hematopoietic cell lineage specificity

Hlf gene modulates hematopoietic cell lineage specificity

A research group has found that when the HLF (hepatic leukemia factor) gene -which is expressed in immature blood cells - does not shut down on time, we are unable to develop a functional long-term immune system. This could be a very early stage of leukemia.

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 can, in turn, be divided into two groups; one that consists of cells with a very short life expectancy and a natural but rather unspecific ability to counteract infections (myeloid cells), and another that, in contrast, consists of very long-lived cells (lymphocytes) that specialize in combatting specific bacteria and viruses.

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. Scientists have searched for genes expressed in immature blood cells but which disappear in connection with their further maturation. They then discovered the HLF gene, which caught their attention for two reasons: one, the gene controls what parts of our DNA are to be used, and two, the gene is directly involved in a rare but very aggressive type of blood cancer.

"Our studies 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, you 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 give rise to a precursor to leukemia. Patients with leukemia in which the HLF gene is involved have a very poor prognosis, but it has been difficult to generate reliable models for studying the emergence, development and possible treatment of these leukemias more thoroughly. The researchers' long-term goal is now to identify the mechanisms that can be used to break down these aggressive leukemias.