Ingredient in pre-clinical treatment for retinal neovascular disease targets gene associated with acute myeloid leukaemia
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 leukaemia cells without harming non-leukemic blood cells.
The results, published today (19 December) in Nature Communications reveal a potential new treatment approach for an aggressive blood cancer with a poor prognosis.
Acute myeloid leukaemia (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 30 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.
“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 leukaemia without harming healthy cells. This shows promise as a potential approach for treating this aggressive leukaemia in humans.”
Dr George Vassiliou, joint leader of the research from the Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute
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.
“Our study describes a novel mechanism required for leukaemia 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.”
Dr Konstantinos Tzelepis, joint lead author from the Wellcome Sanger Institute and University of Cambridge
“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 leukaemia cells growing. The fact that the compound worked so effectively bodes well for its potential development as a new therapy for leukaemia. It will take some time, but there is real promise for a new treatment on the horizon for patients with this aggressive cancer.”
Professor David Bates, from the University of Nottingham and co-founder of biotech company Exonate, which develops eye drops for retinal diseases
Learn more: From eye drops to potential leukaemia treatment
The Latest on: Acute myeloid leukaemia
via Google News
The Latest on: Acute myeloid leukaemia
- Researchers discover potential of antihistamines that cause death of leukemic stem cellson September 6, 2019 at 8:35 pm
Ruth M. Risueño leads the Leukaemic Stem Cell group of the Josep Carreras Leukaemia Research Institute. This group investigates Acute Myeloid Leukaemia (AML) and the cell population responsible for ...
- Antihistamines that cause the death of leukaemic stem cellson September 6, 2019 at 7:25 am
Ruth M. Risueño leads the Leukaemic Stem Cell group of the Josep Carreras Leukaemia Research Institute. This group investigates Acute Myeloid Leukaemia (AML) and the cell population responsible ...
- Two pathways hit with one inhibitoron September 6, 2019 at 1:17 am
Acute myeloid leukemia is an aggressive cancer that can be difficult to treat because of rapidly evolving therapeutic resistance. Melgar et al. focused on a subtype of acute myeloid leukemia ...
- GlycoMimetics: Still Potential In AML Therapyon September 5, 2019 at 9:21 pm
Beyond that, the Phase 3 trial of uproleselan for AML (acute myeloid leukemia) was underway. Then, on August 2, 2019, GlycoMimetics reported failure in the rivipansel trial being conducted by Pfizer.
- Fundraiser to help Nevaeh Nott battling leukaemiaon September 5, 2019 at 7:29 pm
Ms Nott said any money raised would go towards relocation costs and Nevaeh’s medical bills with a small contribution to be made to the Leukaemia Foundation. Nevaeh Nott is fighting her life battling ...
- Outcomes of allogeneic hematopoietic cell transplant for acute myeloid leukemia in adolescent patientson September 5, 2019 at 10:29 am
Patients between 14 and 22 years old are underrepresented in both adult and pediatric studies. We analyzed the outcomes of 94 consecutive patients aged between 14 and 22 who underwent myeloablative ...
- BioXcel Therapeutics Receives FDA Orphan Drug Designation for BXCL701 for the Treatment of Acute Myeloid Leukemia (AML)on September 4, 2019 at 5:00 am
Expansion of clinical development for BXCL701 program planned in hematological malignancies, beyond solid tumors (Pancreatic and tNEPC) Confirmation and further extension of key findings in Nature ...
- Tennis tournament raises funds to help 14-year-old La Grange Park girl with leukemiaon September 3, 2019 at 9:07 am
Mackenzie Ludolph-Koukola, 14, began chemotherapy treatments that day at Lurie Children’s Hospital after being diagnosed with acute myeloid leukemia only days before. “It’s hard,” her father, Jason ...
- Schoolgirl, seven, has bone marrow transplant to help save her older sister from leukaemiaon September 1, 2019 at 2:46 am
Her sister Keira, 13, had been diagnosed with acute myeloid leukaemia in December 2017 which is a rare cancer that only affects 3,100 people each year in the UK. Having gone through countless ...
- Leukemia is not just one diseaseon August 30, 2019 at 3:14 pm
However, not all leukemias are created equal. There are four main types of leukemia. There are 'acute' versus 'chronic' - and there are those that emerge from 'myeloid' versus 'lymphoid' cells. Types ...
via Bing News