A compound being developed to treat eye disease also kills leukemia cells

An active ingredient in eye drops that were being developed for the treatment of a form of eye disease has shown promise for treating an aggressive form of blood cancer. Scientists at the Wellcome Sanger Institute, University of Cambridge, University of Nottingham and their collaborators have found that this compound, which targets an essential cancer gene, could kill leukemia cells without harming non-leukemic blood cells.

The results was published in Nature Communications reveal a potential new treatment approach for an aggressive blood cancer with a poor prognosis.

Acute myeloid leukemia (AML) is a form of blood cancer that affects people of all ages, often requiring months of intensive chemotherapy and prolonged hospital admissions. It develops in cells in the bone marrow crowding out the healthy cells, in turn leading to life-threatening infections and bleeding.

Mainstream AML treatments have remained unchanged for over thirty years, with the current treatment being chemotherapy, and the majority of people's cancer cannot be cured. A subtype of AML, driven by rearrangements in the MLL gene has a particularly bad prognosis.

In a previous study, researchers at the Sanger Institute developed an approach, based on CRISPR gene editing technology, which helped them identify more than 400 genes as possible therapeutic targets for different subtypes of AML. One of the genes, SRPK1, was found to be essential for the growth of MLL-rearranged AML. SRPK1 is involved in a process called RNA splicing, which prepares RNA for translation into proteins, the molecules that conduct the majority of normal cellular processes, including growth and proliferation.

In a new study, Sanger Institute researchers and their collaborators set out to work out how inhibition of SRPK1 can kill AML cells and whether it has therapeutic potential in this disease. They first showed that genetic disruption of SRPK1 stopped the growth of MLL-rearranged AML cells and then went on to study the compound SPHINX31, an inhibitor of SRPK1, which was being used to develop an eye drop treatment for retinal neovascular disease -- the growth of new blood vessels on the retinal surface that bleed spontaneously and cause vision loss.

The team found that the compound strongly inhibited the growth of several MLL-rearranged AML cell lines, but did not inhibit the growth of normal blood stem cells. They then transplanted patient-derived human AML cells into immunocompromised mice and treated them with the compound. Strikingly, the growth of AML cells was strongly inhibited and the mice did not show any noticeable side effects.

Dr George Vassiliou, Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute, said: "We have discovered that inhibiting a key gene with a compound being developed for an eye condition can stop the growth of an aggressive form of acute myeloid leukemia without harming healthy cells. This shows promise as a potential approach for treating this aggressive leukemia in humans."

SRPK1 controls the splicing* of RNA in the production of new proteins. An example of a gene that is affected when SRPK1 is blocked is BRD4, a well-known gene that maintains AML. Inhibiting SRPK1 causes the main form of BRD4 to switch to another form, a change that is detrimental to AML growth.

Dr Konstantinos Tzelepis, the Wellcome Sanger Institute and University of Cambridge, said: "Our study describes a novel mechanism required for leukemia cell survival and highlights the therapeutic potential of SRPK1 inhibition in an aggressive type of AML. Targeting this mechanism may be effective in other cancers where BRD4 and SRPK1 play a role, such as metastatic breast cancer."

Professor David Bates, University of Nottingham and co-founder of biotech company Exonate, which develops eye drops for retinal diseases, said: "When Dr Vassiliou told me that SRPK1 was required for the survival of a form of AML, I immediately wanted to work with him to find out if our inhibitors could actually stop the leukemia cells growing. The fact that the compound worked so effectively bodes well for its potential development as a new therapy for leukemia. It will take some time, but there is real promise for a new treatment on the horizon for patients with this aggressive cancer."

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology,Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

You can submit your abstract on Session or Track : 09. Stem Cells and its Applications

Family tree of blood production reveals hundreds of thousands of stem cells

Adult humans have many more blood-creating stem cells in their bone marrow than previously thought, ranging between 50,000 and 200,000 stem cells. Researchers from the Wellcome Sanger Institute and Wellcome -- MRC Cambridge Stem Cell Institute developed a new approach for studying stem cells, based on methods used in ecology.

The results present a new opportunity for studying, in humans, how stem cells throughout the body change during aging and disease. Using whole genome sequencing to build and analyse a family tree of cells, this work could lead to insights into how cancers develop and why some stem cell therapies are more effective than others.

All of the organs in our body rely on stem cells in order to maintain their function. Adult stem cells found in tissues or organs are a self-sustaining population of cells whose offspring make all of the specialised cell types within a tissue.

Blood stem cells drive the production of blood, and are used in treatments and therapies such as bone marrow transplantations, a treatment for leukemia that replaces cancerous blood cells with healthy blood stem cells.

However, blood stem cells in humans are not fully understood, with even some of the most basic questions, such as how many cells there are and how they change with age, not yet answered.

For the first time, scientists have been able to determine how many blood stem cells are actively contributing in a healthy human. Researchers adapted a method traditionally used in ecology for tracking population size to estimate that a healthy adult has between 50,000 and 200,000 stem cells contributing to their blood cells at any one time.

Dr Peter Campbell, Wellcome Sanger Institute, said: "We discovered that healthy adults have between 50,000 and 200,000 blood stem cells, which is about ten times more than previously thought. Whereas previous estimates of blood stem cell numbers were extrapolated from studies in mice, cats or monkeys, this is the first time stem cell numbers have been directly quantified in humans. This new approach opens up avenues into studying stem cells in other human organs and how they change between health and disease, and as we age."

Scientists found the number of stem cells in the blood increases rapidly through childhood and reaches a plateau by adolescence. The number of stem cells stays relatively constant throughout adulthood.

In the study, researchers conducted whole genome sequencing on 140 blood stem cell colonies from a healthy 59 year-old man. The team adapted a capture-recapture* method, traditionally used in ecology to monitor species populations, to 'tag' stem cells and compare them to the population of blood cells.

"We isolated a number of stem cells from the blood and bone marrow and sequenced their genomes to find mutations. The mutations act like barcodes, each of which uniquely tags a stem cell and its descendants. We then looked for these mutations in the rest of the blood to see what fraction of blood cells carry the same barcodes and from this, we could estimate how many stem cells there were in total." said by Henry Lee-Six, Wellcome Sanger Institute.

Current methods for measuring stem cell population size typically involve genome engineering, meaning they are limited to model organisms, such as mice. By analysing naturally-occurring mutations in human cells, researchers can use the accumulation of mutations to track stem cells to see how stem cell dynamics change over a person's lifetime.

Dr David Kent,Wellcome-MRC Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, said: "This new approach is hugely flexible. Not only can we measure how many stem cells exist, we can also see how related they are to each other and what types of blood cells they produce. Applying this technique to samples from patients with blood cancers, we should now be able to learn how single cells outcompete normal cells to expand their numbers and drive a cancer. As the cost of genomic sequencing comes down, it is transforming scientific research such that studies previously thought to be impossibly large, are now becoming routine. It is a very exciting time to be working in this space."

 Our conference Cell Tissue Science 2019, mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment   and many more. The speakers from different part of the world will be present their immense research talk on this specific topics. We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” .You can also present your latest research at our conference.For more info visit :Cell Tissue Science 2019