Tag Archives: leukemia

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Most common type of childhood leukemia is partly due to lack of exposure to microbes during infancy

British researchers claim they’ve found the likely cause of the most common childhood leukemia. After compiling more than 30 years of research, the team found that acute lymphoblastic leukemia (ALL) is caused by a combination of genetic factors and a lack of exposure to infection during infancy. This means that the disease can be preventable if steps are taken to prime the immune system during the child’s first year of life.

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Credit: Pixabay.

Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell). There are two main types of lymphocytes, B cells and T cells, and in children with ALL, too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These cells do not work like normal lymphocytes and are not able to fight infection very well.

ALL is the most common type of childhood cancer. It most often occurs in children ages 3 to 5 and affects slightly more boys than girls. In the United States, around  3,000 people younger than age 20 are diagnosed with ALL each year. Luckily, research has gone a long way in the past couple of decades, to the point that around 90 percent of cases are cured. However, for more than 100 years scientists have been debating the possible causes for ALL, including ionizing radiation, electricity cables, electromagnetic waves and man-made chemicals. None of these hypotheses have withstood scientific scrutiny.

Now, Professor Mel Greaves and colleagues from The Institute of Cancer Research, London, claim they have finally found out what causes ALL and have evidence to support their claims. According to Greaves, ALL develops due to a two-step genetic mutation before birth in the fetus stage. This mutation predisposes the children to leukemia; however, only 1% of children born with the genetic change go on to develop ALL. The leukemia is triggered later, in childhood, by exposure to one or more infections, which most often happens to be a flu virus infection.  

“This body of research is a culmination of decades of work, and at last provides a credible explanation for how the major type of childhood leukaemia develops. The research strongly suggests that ALL has a clear biological cause, and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukaemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution,” Graves said in a statement.

Studies carried out previously by Greaves and other researchers showed that twins with ALL had to have two mutations in order to develop cancer. The first mutation arises in the womb, leading to the production of a population of pre-malignant cells that spread to the other twin through the shared blood supply. The second mutation occurs after birth and is not present in the other twin. Population studies in people and animal experiments suggest that the second genetic mutation can be triggered by an infection. For instance, mice that had been engineered to have a leukemia-initiating gene went on to develop ALL after they were moved from an ultra-clean, germ-free environment to one that had common microbes.

Studies have shown that microbe exposure early in infancy such as daycare attendance or breastfeeding can offer protection against ALL. Most probably, the exposure to microbes primes the immune system.

Acute lymphoblastic leukemia is particularly prevalent in affluent societies and is increasing in incidence at around 1% per year. The new findings explain why this may be happening: a lack of microbial exposure can lead to an immune system malfunction that can trigger ALL. So, the problem is that a lack of infection can lead to a far more threatening infection later in life.

Now, Greaves and colleagues are investigating whether earlier exposure to harmless bugs could prevent this cancer in mice. If this happens, then ALL prevention measures could be taken such as exposing children to common but benign microbes.

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies – perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs’,” said Greaves.

“It’s exciting to think that, in future, childhood leukemia could become a preventable disease as a result of this work. Preventing childhood leukemia would have a huge impact on the lives of children and their families in the UK and across the globe,” said Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London.

Scientific reference: Mel Greaves, A causal mechanism for childhood acute lymphoblastic leukaemia, Nature Reviews Cancer (2018). DOI: 10.1038/s41568-018-0015-6.

Leukemia drug found to dramatically boost immune system

A class of drugs currently used to treat leukemia has been found to have some severe side effects – positive ones, that is. The drug was found to drastically boosting immune responses against many different cancers, reports a new study.

The drug class is referred to as p110´ inhibitors. Recently, it has been used with significant success against certain leukemias in recent clinical trials; patients were given a placebo, and after a while, they were given the actual drug – and it started to work right away. However, until now, it hasn’t been tested against other cancers.

The new study, which was published in Nature, shows that p110δ inhibitors have remarkable effects against a broad range of cancers, especially reducing the chance of relapse. Basically, these drugs inhibit the p110δ enzyme, boosting the body’s immune system, enabling it to kill more tumor cells.

“Our study shows that p110δ inhibitors have the potential to offer effective immunity to many types of cancer by unleashing the body’s own immune response,” says study co-leader Professor Bart Vanhaesebroeck of the UCL Cancer Institute, who first discovered the p110δ enzyme in 1997. “p110δ is highly expressed and important in white blood cells, called ‘leukocytes’. Given that leukemias are the result of leukocytes becoming cancerous, they are a natural target for p110δ inhibitors. Now, we have shown that blocking p110δ also has the remarkable effect of boosting the body’s immune response against leukemias as well as other cancers.”

Initially, they tested it on mice, and the results were very exciting. However, many drugs which have good results in mice don’t work that well in humans – which is why this study is particularly interesting. ollowing p110δ inhibition, the immune system develops a sort of memory, enabling it to be more efficient with cancer in future battles, massively reducing relapse rates.

An electron scan of T-cells. Image via Wikipedia.

“Our work shows that p110δ inhibitors can shift the balance from the cancer becoming immune to our body’s defenses towards the body becoming immune to the cancer, by disabling regulatory T cells,” says study co-leader Dr Klaus Okkenhaug of the Babraham Institute. “This provides a rationale for using these drugs against both solid and blood cancers, possibly alongside cancer vaccines, cell therapies and other treatments that further promote tumor-specific immune responses.”

Aside for having obvious potential applications, this study also raises some questions about how the body fights against cancers. The gene p110δ regulates immune function; the enzyme is especially important for the regulation of T-cells, a type of white blood cells which play a crucial role in cell-mediated immunity. What they describe in this study is that P110δ inhibition reshapes the body’s immune system; regulatory T-cells become inactive, and instead a sub-population of T-cells, CD8+ cytotoxic T-cells become hyper-activated and hunt down and kill any rogue cancer cells lying around the body which may cause cancerous relapse to happen. It’s still not entirely clear why this is happening – the beauty and the curse of science.

Scientific Reference: Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature, 2014; DOI: 10.1038/nature13444

 

Scientists Finds Possible Cure for Leukemia from Fish Oil

A compound derived from fish oil is found to provide an effective remedy for leukemia, known as the cancer of white blood cells.

Encouraged by successful experiments on  mice, the researchers applied for a patent of the compound and are now preparing to test it on human beings.

The scientists are examining its efficacy in treating the terminal stage of leukemia, known as the ‘Blast Crisis” for which there is no drug available.

The study was led by an Indian born scientist, Sandeep Prabhu, associate professor of immunology and molecular toxicology in the Department of Veterinary and Medical Sciences, Penn State (USA).

The compound, identified as delta-12-protaglandin J3, or D12-PGJ3 – is produced from EPA — Eicosapentaenoic Acid — an Omega-3 fatty acid found in fish and in fish oil, Dr.Prabhu said.

“Research in the past on fatty acids has shown the health benefits of fatty acids on cardiovascular system and brain development, particularly in infants. But we have shown that some metabolites of Omega-3 have the ability to selectively kill the leukemia-causing stem cells in mice,” said Prabhu.

“The important thing is that the mice were completely cured of leukemia with no relapse.”   The findings were released in the current issue of Blood.

The compound kills cancer-causing stem cells in the mice’s spleen and bone marrow. Specifically, it activates a gene — p53 — in the leukemia stem cell that programs the cell’s own death.

“p53 is a tumor suppressor gene that regulates the response to DNA damage and maintains genomic stability,” Prabhu said.

But p53 has more going to it: apparently, it also determines how big your organs will get and has potential to treat other cancers as well.

Killing the stem cells in leukemia, a cancer of the white blood cells, is important because stem cells can divide and produce more cancer cells, as well as create more stem cells, Prabhu said.

The current method of treatment prolongs the life of the victim with many relapses without providing permanent cure. If they stop the drugs, the drug-resistant disease relapses as the drug can not kill the diseased stem cells for good in the human body.

In the year 2000, approximately 256,000 children and adults around the world developed some form of leukemia, and 209,000 died of it. About 90% of all leukemias are diagnosed in adults.