The HLF-gene controls the generation of our long-term immune system

November 22, 2017

A research group at Lund University in Sweden 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 give rise to all of our blood cells: the that transport oxygen, the platelets that enable blood coagulation, and our 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 (), and another that, in contrast, consists of very long-lived cells (lymphocytes) that specialise in combatting specific bacteria and viruses.

"The ability of to form all types of blood cells is a fundamental property that is also utilised in connection with . An increased understanding of these processes is crucial as immune cells in patients who undergo bone marrow transplants are regenerated very slowly, which results in a long period of immune sensitivity," says 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. David Bryder and his colleagues 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 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.

"The knowledge and experimental model systems we developed concerning how HLF affects cell development enables us to map the order of gene mutations that lead to HLF-generated leukemia, which is an important next step towards our goal," concludes David Bryder.

Explore further: How blood can be rejuvenated

More information: Critical Modulation of Hematopoietic Lineage Fate by Hepatic Leukemia Factor. DOI: dx.doi.org/10.1016/j.celrep.2017.10.112

Related Stories

How blood can be rejuvenated

February 23, 2017
Our blood stem cells generate around a thousand billion new blood cells every day. But the blood stem cells' capacity to produce blood changes as we age. This leads to older people being more susceptible to anaemia, lowered ...

Bacterial infection stresses hematopoietic stem cells

August 24, 2017
It has been thought that only immune cells would act as the line of defense during bacterial infection. However, recent research has revealed that hematopoietic stem cells, cells that create all other blood cells throughout ...

Researchers show how a protein prevents the uncontrolled expansion of immune cells

June 22, 2017
The mammalian immune system consists of millions of individual cells that are produced daily from precursor cells in the bone marrow. During their development, immune cells undergo a rapid expansion, which is interrupted ...

Rare form of leukemia found to originate in stem cells

February 13, 2014
(Medical Xpress)—An international team of researchers working out of the University of Toronto has found that one type of rare leukemia appears to get its start in stem cells. In their paper published in the journal Nature, ...

An epigenetic lesion could be responsible for acute T-cell leukemia

March 30, 2017
Researchers from the Epigenetics and Cancer Biology Program (PEBC) led by Dr. Manel Esteller at the Bellvitge Biomedical Research Institute (IDIBELL) have discovered how an epigenetic lesion can lead to T-cell acute lymphoblastic ...

Aggressiveness of acute myeloid leukemia elucidated

June 24, 2016
Antoine Peters and colleagues at the Basel University Children's Hospital (UKBB) have discovered why acute leukemias with the same genetic abnormality vary in their aggressiveness based on their cellular origin. They found ...

Recommended for you

Association found between abnormal cerebral connectivity and variability in the PPARG gene in developing preterm infants

December 12, 2017
(Medical Xpress)—A team of researchers with King's College London and the National Institute for Health Research Biomedical Research Centre, both in the U.K., has found what they describe as a strong association between ...

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.