Tag: leukaemia

Categories : Cancer PaediatricsTags :

Childhood Leukaemia Aggressiveness Depends on Timing of Genetic Mutation

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Credit: National Cancer Institute

A team of researchers at the Icahn School of Medicine at Mount Sinai has uncovered why children with the same leukaemia-causing gene mutation can have dramatically different outcomes: it depends on when in development the mutation first occurs.  

The study, led by Elvin Wagenblast, PhD, Assistant Professor of Oncological Sciences, and Pediatrics, at the Icahn School of Medicine at Mount Sinai, was published in Cancer Discovery. It shows that leukemia beginning before birth is often more aggressive, grows faster, and is harder to treat. This adds a missing dimension to precision medicine for childhood leukaemia. 

Dr. Wagenblast and his team at the Wagenblast Lab set out to answer a central question about how a normal blood stem cell can become cancerous. They applied cutting-edge CRISPR/Cas9 genome-editing approaches in human primary blood stem cells to model different developmental stages of acute myeloid leukaemia, one of the most aggressive types of blood cancer. 

Using CRISPR technology, the team induced the NUP98::NSD1 fusion oncoprotein, a cancer-promoting protein created when two genes abnormally fuse, into human blood stem cells from multiple developmental stages, ranging from prenatal to postnatal, adolescence, and adulthood. This approach created the first humanised experimental model that tracks how the same mutation behaves differently depending on when in life it arises. 

The results were striking: stem cells produced during prenatal development transformed easily into leukaemia, creating a highly aggressive and more primitive form of leukaemia. Stem cells produced postnatally became increasingly resistant to transformation and required additional mutations to become cancerous. Prenatal-origin leukaemia stem cells, which are abnormal blood stem cells that arise before birth and can cause certain childhood leukaemias, were more dormant (quiescent) and relied heavily on certain energy sources specific to the cancer state, which were not seen in the leukaemias that originated later in life. Although these prenatal leukaemia stem cells were more dormant, this quiescent state makes them harder to eliminate with standard treatments, helping explain why prenatal-origin leukaemias behave more aggressively, despite identical genetics. 

By analysing single-cell gene expression data from their models, the investigators identified a prenatal gene signature that predicts whether a child’s leukaemia likely began before birth. In patients, this signature strongly correlated with significantly worse clinical outcomes. 

“This work tells us that age matters at the cellular level,” said Dr Wagenblast. “The same mutation behaves very differently depending on when it happens. Understanding this gives us a new way to identify the highest-risk patients and to tailor therapies that go beyond standard genetic classifications.” 

The team tested therapies against the most aggressive leukaemia stem cells and discovered that these cells were especially vulnerable to venetoclax, a Food and Drug Administration-approved drug already used in the clinic. Venetoclax-based combinations, including with standard chemotherapy, significantly reduced aggressiveness in the experimental models. 

“These findings give clinicians mechanistic support to use venetoclax combinations in NUP98-rearranged acute myeloid leukaemia, particularly in younger patients whose disease likely started before birth,” said Dr Wagenblast. 

Understanding when leukaemia begins may help doctors choose more effective therapies earlier, reducing trial-and-error approaches and preventing resistance and relapse later on. 

Conceptually, the study shifts how scientists understand childhood cancer. The developmental timing of the first mutation is not a minor detail. It fundamentally shapes disease biology, treatment resistance, and relapse risk. 

The research opens the door to new diagnostic tools that can identify prenatal-origin leukaemias, venetoclax-based combination therapies that more precisely target vulnerable leukaemia stem cells, and clinical trials that incorporate developmental timing into risk assessment. 

Next, the team plans to develop therapies that more directly target the metabolic program unique to prenatal-origin leukaemias, with the goal of selectively eliminating leukaemia stem cells while sparing healthy blood stem cells. 

Source: Mount Sinai

Categories : CancerTags :

‘Wondrous’ Drug to Treat Aggressive Leukaemia Gets UK Approval

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Killer T cells surround a cancer cell. Credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, National Institutes of Health (CC BY 2.0).

Adult patients with an aggressive form of leukaemia will be able to receive a breakthrough immunotherapy, which was invented by University College London researchers, on the NHS within weeks following approval for use by the UK’s National Institute for Health and Care Excellence (NICE).

The CAR T-cell therapy – known as ‘obe-cel’ and marketed as Aucatzyl – involves taking a patient’s immune cells and reprogramming them in a lab to identify and target their cancer, before returning them to the body as ‘living medicine’.

Obe-cel is a second-generation CAR T cell therapy invented by scientists from the UCL Cancer Institute, led by Dr Martin Pule, and has delivered promising results in treating patients with acute lymphoblastic leukaemia (ALL), an aggressive blood cancer.

The therapy has reduced immune toxicity and persists for longer in blood cancer patients, overcoming two common limitations of earlier CAR T cell therapies. Aucatzyl was taken through clinical trials and is manufactured by UCL spinout business Autolus, which was set up with the help of UCL Business, the commercialisation company of UCL.

The development of CAR T cell therapy has had long-standing support from the National Institute for Health and Care Research (NIHR) UCLH Biomedical Research Centre (BRC).

NHS England today announced that the personalised therapy would be available on the NHS within weeks through specialist centres.

Dr Claire Roddie, one of the team who developed the treatment from UCL Cancer Institute and UCLH consultant haematologist, said: “I am delighted to hear of NICE’s decision. Many more patients now stand to benefit from CAR-T cell therapy on the NHS. 

“We have been working on proving the safety and efficacy of this drug since 2017 and it has brought together clinical and research teams from UCL and UCLH, with support from government and arm’s-length bodies like the NIHR and the BRC as well as the pharmaceutical industry.

“The many, many people involved in this work can feel immensely proud of this achievement which will help save the lives of many more patients.”

Eligible patients will receive two doses of CAR-T therapy intravenously, ten days apart, with the treatment being delivered at specialist CAR-T centres across the country.

The treatment will be available to people aged 26 and over with B-cell acute lymphoblastic leukaemia which has returned or not responded to previous treatment. 

It is estimated that it could be administered to around 50 patients each year in England.

In a clinical trial, 77% of patients saw their cancer enter remission after treatment with obe-cel, with half of those showing no signs of detectable cancer after three and a half years. 

The treatment – which has been researched, developed and manufactured in the UK – was also found to have lower toxicity and was less likely to cause serious side effects than other CAR (chimeric antigen receptor) T-cell therapies.

Dr Anne Lane, UCL Business CEO, said: “This cutting-edge personalised immunotherapy has been on a 10-year journey starting with research by clinical academics in UCL’s Cancer Institute who, with the support of UCL Business, established Autolus, a spinout company dedicated to developing, trialling and bringing AUCATZYL® to market. That journey has required vision, tenacity and over £800m. Today that has hugely paid off and will benefit people across the UK. It’s an inspiring demonstration of what can be achieved when university academics, NHS hospitals and investors work together.”

Professor Peter Johnson, NHS National Clinical Director for Cancer, said: “This cutting-edge therapy has shown real promise in trials and could give patients with this aggressive form of leukaemia a chance to live free from cancer for longer – and, for some, it could offer the hope of a cure.

“This ‘living medicine’ boosts a patient’s own immune system and then guides T-cells towards the cancer to kill it – it is fantastic to have another pioneering option available on the NHS, adding to our range of CAR-T therapies which are helping people with blood cancers live longer, healthier lives.”

Harry, a 19-year-old student from Harrogate, was treated with obe-cel for B-cell ALL as part of a clinical trial in 2024. He said: “I feel so lucky to have had access to such a wondrous treatment. Not only did it work better than my doctors thought it would, it worked without many of the horrible side effects you can get from other treatments.

“I think it’s brilliant obe-cel is now available on the NHS for people over the age of 26. The biggest thing it offers is hope. When you’re facing a situation like mine, hope is the most valuable thing you can have.”

Health Minister Ashley Dalton said: “This pioneering treatment is excellent news for patients and their families, demonstrating how the NHS is at the forefront of medical innovation.

“Our 10 Year Health Plan is about harnessing our world-leading life sciences sector to deliver treatments like this – innovative therapies that save lives.

“By supporting new treatments with fewer side effects and shorter hospital stays, we’re building an NHS fit for the future whilst cementing the UK’s position as a global leader in medical research.”

Fiona Bride, interim Chief Commercial Officer and Director of Medicines Value & Access at NHS England, said: “This is a success story that’s made in Britain, and shows how collaboratively we can bring to life the ambition of the 10 Year Health Plan, showcasing how the UK’s competitive edge in life sciences can translate to better outcomes and treatments for NHS patients.

“The journey of obe-cel from scientific research in a UK university to a safe, clinically and cost-effective treatment set to be delivered through the NHS specialist CAR-T network is a remarkable one and I am grateful to colleagues who have played their part along the way.”  

Acute lymphoblastic leukaemia is an aggressive cancer in the blood and bone marrow, with around 800 people being diagnosed in the UK every year, around half of which are in adults.

Data shows patients with aggressive forms of the cancer receiving chemotherapy, the current routine standard of care, live for just 10 months on average after treatment.

The therapy will be fast tracked to patients more quickly than the standard 90-day implementation period thanks to interim funding from the NHS’s Cancer Drugs Fund.

Source: University College London

Categories : CancerTags :

Tough Enough to Save a Life? SA Athletes Challenge Men to Register as Stem Cell Donors

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Jaco Pretorius was inspired by his best friend’s life being saved by a stem cell transplant.

With South African men having a 20-50% higher incidence rate of blood cancers than women, sports icons Jaco Pretorius, Seabelo Senatla, and Temba Bavuma are leveraging their platforms to challenge more men to join the stem cell registry and help rewrite the odds for patients in need.

The challenge confronts a widespread public disconnect from the issue. “Many people seem to be disinterested, until one of their own is diagnosed,” notes Senatla. “People tend to be nonchalant when things don’t pertain to them; they have this attitude of ‘not my problem’.”

Pretorius agrees that a lack of awareness is a major hurdle. “My experience is that people are not aware of the great need in our country and the simplicity of the process. But we’ve seen so many times how sport has the power to unite South Africa. When athletes from different backgrounds set an example, I believe people will follow, and together we can make a real difference.”

His advocacy is rooted in his own firsthand experience. Motivated to register after his best friend’s life was saved by a transplant, he was later called upon to donate. He hopes sharing his story will dismantle common fears. “The perception is that it is a painful procedure which carries personal risk. My experience was the complete opposite.”

A concern Bavuma often hears about is the time commitment, especially for those with demanding jobs or family responsibilities. “But if you do get the call to donate, those few days potentially add years, even decades, to someone else’s life. That’s a trade any of us should be willing to make.”

Tackling a common myth, Senatla says, “One of the biggest myths I’ve had to debunk is people having the notion that since stem cells are taken from them, they’ll be left with fewer stem cells. The body of a healthy person is constantly producing stem cells. You’re not in danger of having too little if you donate some to someone.”

For him, the motivation to act is deeply personal. “I grew up in an environment in which I was made to understand that your gifts are not only for you. Other people must benefit as well. That’s what’s in practice here.”

Addressing men who might be hesitant, Senatla points out that they aren’t losing anything by registering. “Rather, they’re affording someone who is ill a second chance at life.”

Bavuma challenges the passive mindset. “In cricket, you can’t field, thinking someone else will take the catch. The same goes for this. Too many people assume there are enough donors already, or that someone else will register.”

Pretorius adds, “I would encourage other people to immediately take action. The process is pain-free, professional, non-invasive, and there are no financial implications – only your time and commitment.”

The outcome of his simple act was profound. “I received communication from the stem cell recipient that the transplant was successful, and the person is healthy and well. That was one of the best feelings – to know that through such a simple action, someone else’s life was saved.”

Palesa Mokomele, Head of Community Engagement and Communications at DKMS Africa, highlights the impact of these role models. “While men currently make up the majority of registered donors in South Africa, the overall pool of donors is critically low compared to the national need. Having respected public figures like Jaco, Seabelo, and Temba lead this conversation is invaluable. When men see other men stepping up, it directly challenges hesitation, shifts perceptions, and ultimately helps save lives.”

Senatla offers a reminder of our shared humanity. “You’re never too important to help, and you should help because you can. Being in a position to help is an absolute privilege.”

“This isn’t a spectator sport; everyone who can help needs to get in the game,” concludes Bavuma.

South Africans aged 17 to 55 who are in good health can register as potential stem cell donors. The process is simple and starts with an online registration and a cheek swab.

Register today at https://www.dkms-africa.org/save-lives.

Categories : Ageing CancerTags :

Global Study Challenges Age-Based Treatment Decisions in Leukaemia

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Study of 2,800 patients suggests moving beyond chronological cut-offs in cancer care

SAG Leukaemia. Credit: Scientific Animations CC0

An international study conducted by the Alliance for Clinical Trials in Oncology and the Acute Myeloid Leukemia Cooperative Group reveals that age-based classifications in the treatment of acute myeloid leukaemia (AML) may be outdated and overly simplistic.

AML is a fast-growing cancer of the blood and bone marrow that disproportionately affects older adults. Historically, age has been a key factor in determining treatment intensity, eligibility for clinical trials, and access to targeted therapies. However, this new research suggests that age alone is not a reliable indicator of disease biology or prognosis.

“Our findings support a more flexible, biology-driven approach to AML treatment and trial design. Age alone should not be a gatekeeper to potentially life-saving therapies,” said Alliance researcher and lead author Ann-Kathrin Eisfeld, MD, associate professor of Internal Medicine and director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University. “Our results suggest reconsidering age-based eligibility criteria for treatments. By focusing on molecular and genetic profiles rather than chronological age, clinicians may better tailor treatments to individual patients, improving outcomes and expanding access to novel therapies.”

Published in Leukemia, the study analysed data from 2823 adult AML patients treated in the setting of large cooperative group frontline trials across the United States (CALGB/Alliance) and Germany (AMLCG), uncovering nuanced age-related trends in genetic mutations and survival outcomes that challenge current clinical practices. This research is the first large-scale, cross continental study to analyse the mutational patterns and outcomes among patients of all age groups with AML.

The analysis included patients treated with frontline cytarabine-based chemotherapy between 1986 and 2017. Molecular profiling was conducted using targeted sequencing platforms, and survival outcomes were assessed using the 2022 European LeukemiaNet (ELN) genetic-risk classification.

The study found no clear age threshold that could biologically or prognostically separate patients into distinct groups. Instead, genetic mutations and survival outcomes varied continuously across the age spectrum. This challenges the long-standing practice of using arbitrary age cut-offs, such as 60 or 65 years, to guide treatment decisions.

Survival outcomes also declined steadily with age, even among patients classified as having favourable genetic risk. For example, patients aged 18 to 24 with favourable-risk AML had a five-year overall survival rate of 73%, while those aged 75 and older had a survival rate of just 21%. This trend was consistent across all risk categories, indicating that age negatively impacts prognosis regardless of genetic classification.

“This research arrives at a critical moment in oncology, as precision medicine continues to transform cancer care,” added Dr Eisfeld. “Most targeted treatment options are still only available for patients above a certain age threshold that is dictated by corresponding inclusion criteria of pivotal clinical trials, even though patients outside of that age range might equally benefit from these often less toxic treatments.”

Source: Alliance for Clinical Trials in Oncology

Categories : Cancer New Compounds and TreatmentsTags :

Aspergillus Flavus: From the ‘Curse of Tutankhamun’ to New Cancer Treatment

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A sample of Aspergillus flavus cultured in the Gao Lab. (Credit: Bella Ciervo)

University of Pennsylvania-led researchers have turned a deadly fungus into a potent cancer-fighting compound. After isolating a new class of molecules from Aspergillus flavus, a toxic crop fungus linked to deaths in excavating ancient tombs, the researchers modified the chemicals and tested them against leukaemia cells. The result was a promising cancer-killing compound that rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines.

“Fungi gave us penicillin,” says Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in Bioengineering (BE) and senior author of a new paper in Nature Chemical Biology on the findings. “These results show that many more medicines derived from natural products remain to be found.”

From Curse to Cure

A. flavus, named for its yellow spores, has long been a microbial villain. After archaeologists opened King Tutankhamun’s tomb in the 1920s, a series of untimely deaths among the excavation team fuelled rumours of a pharaoh’s curse. Decades later, doctors theorised that fungal spores, dormant for millennia, could have played a role.

In the 1970s, a dozen scientists entered the tomb of Casimir IV in Poland. Within weeks, 10 of them died. Later investigations revealed the tomb contained A. flavus, whose toxins can lead to lung infections, especially in people with compromised immune systems.

Now, that same fungus is the unlikely source of a promising new cancer therapy.

A Rare Fungal Find

The therapy in question is a class of ribosomally synthesised and post-translationally modified peptides, or RiPPs, pronounced like the “rip” in a piece of fabric. The name refers to how the compound is produced – by the ribosome, a tiny cellular structure that makes proteins – and the fact that it is modified later, in this case, to enhance its cancer-killing properties.

“Purifying these chemicals is difficult,” says Qiuyue Nie, a postdoctoral fellow in CBE and the paper’s first author. While thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. In part, this is because past researchers misidentified fungal RiPPs as non-ribosomal peptides and had little understanding of how fungi created the molecules. “The synthesis of these compounds is complicated,” adds Nie. “But that’s also what gives them this remarkable bioactivity.”

Hunting for Chemicals

To find more fungal RiPPs, the researchers first scanned a dozen strains of Aspergillus, which previous research suggested might contain more of the chemicals.

By comparing chemicals produced by these strains with known RiPP building blocks, the researchers identified A. flavus as a promising candidate for further study.

Genetic analysis pointed to a particular protein in A. flavus as a source of fungal RiPPs. When the researchers turned the genes that create that protein off, the chemical markers indicating the presence of RiPPs also disappeared.

This novel approach – combining metabolic and genetic information – not only pinpointed the source of fungal RiPPs in A. flavus, but could be used to find more fungal RiPPs in the future.

A Potent New Medicine

After purifying four different RiPPs, the researchers found the molecules shared a unique structure of interlocking rings. The researchers named these molecules, which have never been previously described, after the fungus in which they were found: asperigimycins.

Even with no modification, when mixed with human cancer cells, asperigimycins demonstrated medical potential: two of the four variants had potent effects against leukaemia cells.

Another variant, to which the researchers added a lipid found in bees’ royal jelly, performed as well as cytarabine and daunorubicin, two FDA-approved drugs that have been used for decades to treat leukaemia.

Cracking the Code of Cell Entry

To understand why lipids enhanced asperigimycins’ potency, the researchers selectively turned genes on and off in the leukaemia cells. One gene, SLC46A3, proved critical in allowing asperigimycins to enter leukaemia cells in sufficient numbers.

That gene helps materials exit lysosomes, the tiny sacs that collect foreign materials entering human cells. “This gene acts like a gateway,” says Nie. “It doesn’t just help asperigimycins get into cells, it may also enable other ‘cyclic peptides’ to do the same.”

Like asperigimycins, those chemicals have medicinal properties – nearly two dozen cyclic peptides have received clinical approval since 2000 to treat diseases as varied as cancer and lupus – but many of them need modification to enter cells in sufficient quantities.

“Knowing that lipids can affect how this gene transports chemicals into cells gives us another tool for drug development,” says Nie.

Disrupting Cell Division

Through further experimentation, the researchers found that asperigimycins likely disrupt the process of cell division. “Cancer cells divide uncontrollably,” says Gao. “These compounds block the formation of microtubules, which are essential for cell division.”

Notably, the compounds had little to no effect on breast, liver or lung cancer cells – or a range of bacteria and fungi – suggesting that asperigimycins’ disruptive effects are specific to certain types of cells, a critical feature for any future medication.

Future Directions

In addition to demonstrating the medical potential of asperigimycins, the researchers identified similar clusters of genes in other fungi, suggesting that more fungal RiPPS remain to be discovered. “Even though only a few have been found, almost all of them have strong bioactivity,” says Nie. “This is an unexplored region with tremendous potential.”

The next step is to test asperigimycins in animal models, with the hope of one day moving to human clinical trials. “Nature has given us this incredible pharmacy,” says Gao. “It’s up to us to uncover its secrets. As engineers, we’re excited to keep exploring, learning from nature and using that knowledge to design better solutions.”

Source: University of Pennsylvania School of Engineering and Applied Science

Categories : Cancer General InterestTags :

Immune System the Focus of PhD’s Research at UKZN

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Elated at graduating with a doctoral degree is Dr Aviwe Ntsethe. Credit: University of KwaZulu-Natal

Dr Aviwe Ntsethe’s curiosity in the Medical field deepened when he started exploring the complexities of human physiology and the crucial role of the immune system in cancer, leading to him graduating with a PhD.

Growing up in the small town of Bizana in the Eastern Cape, Ntsethe attended Ntabezulu High School, where his passion for Medical Science took root. Despite facing significant challenges, including limited funding opportunities for his studies, he remained determined to advance in the discipline.

Throughout his PhD journey at UKZN, Ntsethe had to juggle multiple jobs to support himself and his studies while conducting his research. He worked at Netcare Education and the KwaZulu-Natal College of Emergency Care, and later took up a position as a contractual laboratory technician in the Department of Physiology at UKZN. It was with the guidance of his PhD supervisor, Professor Bongani Nkambule, that he learned critical work ethics and advanced laboratory techniques. The co-supervision of Professor Phiwayinkosi Dludla further enriched his research experience and contributed to his academic growth.

Ntsethe’s thesis focused on investigating B cell function and immune checkpoint expression in patients with Chronic Lymphocytic Leukaemia (CLL). The study found that patients with CLL had higher levels of immune checkpoint proteins in their B cell subsets, which play a crucial role in regulating the immune system.

Furthermore, using monoclonal antibodies that target these immune checkpoints, he found these patients could potentially benefit from immunotherapy. Specifically, immunotherapy may improve the function of B cells, key players in fighting infections and cancers, thereby offering new hope for better outcomes in patients with CLL.

He has published three papers from this study. ‘I am excited and proud when I reflect on my achievement of completing this significant journey which was both challenging and rewarding, pushing me to expand my knowledge and skills in ways I never imagined.’

Now, a lecturer at Nelson Mandela University, Ntsethe is committed to mentoring the next generation of Medical scientists. He continues to use the invaluable knowledge and experience he gained during his PhD studies to inspire students and cultivate their passions in research and health sciences. Looking ahead, Ntsethe hopes to expand his research, focusing on immune system interactions in chronic diseases while also encouraging students from diverse backgrounds to pursue careers in Medical Science.

Outside academia, Ntsethe enjoys travelling, staying physically active through workouts, playing chess and indulging in coding or programming.

Source: University of KwaZulu-Natal

Categories : CancerTags :

New Study Reveals Why Common Leukaemia Treatments Fail in Some Patients

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Genetic mutations and cell maturity as key factors in acute myeloid leukaemia drug resistance

Photo by Tima Miroshnichenko on Pexels

An international study led by the University of Colorado Cancer Center has uncovered why a widely used treatment for acute myeloid leukaemia (AML) doesn’t work for everyone. The findings could help doctors better match patients with the therapies most likely to work for them.

The study was published in Blood Cancer Discovery.

Researchers analysed data from 678 AML patients, the largest group studied to date for this treatment, and found that both gene mutations and the maturity of leukaemia cells affect how patients respond to a drug combination of venetoclax and hypomethylating agents (HMA).

“Venetoclax-based therapies are now the most common treatment for newly diagnosed AML,” said Daniel Pollyea, MD, MS, professor of medicine at University of Colorado. “But not all patients respond the same way. Our goal was to figure out why and give doctors better tools to predict outcomes at the start.”

Mutations and maturity of leukaemia cells

AML is a fast-growing cancer of the blood and bone marrow, most often seen in older adults. Many patients can’t tolerate traditional chemotherapy, so doctors treat them with venetoclax plus HMA. This combination has improved survival for many, but some patients still relapse or don’t respond.

The study found that patients with a certain type of AML, called “monocytic,” had worse outcomes especially if they did not have a helpful gene mutation known as NPM1. These patients were also more likely to carry other mutations, such as KRAS, that are linked to drug resistance.

“Patients with monocytic AML and no NPM1 mutation were nearly twice as likely to die from the disease,” said Pollyea. “So, it’s not just about the gene mutations. It’s also about how developed or mature the cancer cells are when treatment begins.”

Previous research often focused only on either genetic mutations or cell type. Pollyea’s team looked at both, giving them a clearer understanding of how these two factors work together to influence treatment response.

Designing therapies that shut down cancer cell escape routes

“We learned that some cancer cells basically find a back door to evade the treatment,” said Pollyea. “By identifying how and why that happens, we can begin designing therapies that shut down those escape routes.”

This is a powerful new way to classify AML patients by risk, enabling doctors to better predict who is likely to respond to venetoclax and who might need another approach.

“This is a major step toward personalised medicine in AML,” said Pollyea. “We’re moving closer to a world where we can look at a patient’s leukaemia on day one and know which therapy gives them the best chance and ultimately improve survival rates.”

Pollyea and his team are working to expand the study with even more patient data and hope to design a clinical trial that uses this model to guide treatment decisions.

Source: University of Colorado Anschutz Medical Campus

Categories : CancerTags :

A Downside of Taurine: It Drives Leukaemia Growth

On By Peter Van Dyk
SAG Leukaemia. Credit: Scientific Animations CC0

A new scientific study identified taurine, which is made naturally in the body and consumed through some foods, as a key regulator of myeloid cancers such as leukaemia, according to a paper published in the journal Nature.

The preclinical research shows that scientists are a step closer to finding new ways to target leukaemia, which is one of the most aggressive blood cancers. The Wilmot Cancer Institute investigators at the University of Rochester were able to block the growth of leukaemia in mouse models and in human leukaemia cell samples by using genetic tools to prevent taurine from entering cancer cells.

Led by Jeevisha Bajaj, PhD, the research team discovered that taurine is produced by a subset of normal cells in the bone marrow microenvironment, the tissue inside bones where myeloid cancers begin and expand. Leukaemia cells are unable to make taurine themselves, so they rely on a taurine transporter (encoded by the SLC6A6 gene) to grab taurine from the bone marrow environment and deliver it to the cancer cells.

The discovery occurred as scientists were mapping what happens within the bone marrow and its ecosystem—a longtime focus among Wilmot researchers, who have advanced the science around the microenvironment with the goal of improving blood cancer treatments.

“We are very excited about these studies because they demonstrate that targeting uptake by myeloid leukaemia cells may be a possible new avenue for treatment of these aggressive diseases,” said Bajaj, an assistant professor in the Department of Biomedical Genetics and a member of Wilmot’s Cancer Microenvironment research program.

Researchers also discovered that as leukaemia cells drink up taurine, it promotes glycolysis (a breakdown of glucose to produce energy) to feed cancer growth. Prior to this, the authors said, it was not known that taurine might have a cancer-promoting role.

Leukaemia has several subtypes and survival rates vary. This study finds that taurine transporter expression is essential for the growth of multiple subtypes including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), and myelodysplastic syndromes (MDS), which all originate from blood stem cells in the bone marrow. Future studies will investigate signals from the microenvironment that promote the transition of MDS, a precursor to leukaemia, to acute leukaemia.

Source: University of Rochester Medical Center

Categories : CancerTags :

Research Identifies Beneficial Genetic Changes in Regular Blood Donors

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Photo by Charliehelen Robinson on Pexels

Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells.

Understanding the differences in the mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers develop and hopefully how to intervene before the onset of clinical symptoms.

As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the emergence of clones, which are groups of blood cells that have a slightly different genetic makeup. Sometimes, specific clones can lead to blood cancers like leukaemia.

When people donate blood, stem cells in the bone marrow make new blood cells to replace the lost blood and this stress drives the selection of certain clones.

Blood donation impacts makeup of cell populations

In research published in Blood, the team at the Crick, in collaboration with scientists from the DKFZ in Heidelberg and the German Red Cross Blood Donation Centre, analysed blood samples taken from over 200 frequent donors – (three donations a year over 40 years, more than 120 times in total) – and sporadic control donors who had donated blood less than five times in total.

Samples from both groups showed a similar level of clonal diversity, but the makeup of the blood cell populations was different.

For example, both sample groups contained clones with changes to a gene called DNMT3A, which is known to be mutated in people who develop leukaemia. Interestingly, the changes to this gene observed in frequent donors were not in the areas known to be preleukaemic.

A balancing act

To understand this better, the Crick researchers edited DNMT3A in human stem cells in the lab. They induced the genetic changes associated with leukaemia and also the non-preleukaemic changes observed in the frequent donor group.

They grew these cells in two environments: one containing erythropoietin (EPO), a hormone that stimulates red blood cell production which is increased after each blood donation, and another containing inflammatory chemicals to replicate an infection.

The cells with the mutations commonly seen in frequent donors responded and grew in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was seen in the cells with mutations known to be preleukaemic.

This suggests that the DNMT3A mutations observed in the frequent donors are mainly responding to the physiological blood loss associated with blood donation.

Finally, the team transplanted the human stem cells carrying the two types of mutations into mice. Some of these mice had blood removed and then were given EPO injections to mimic the stress associated with blood donation.

The cells with the frequent donor mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. In sharp contrast, the preleukaemic mutations drove a pronounced increase in white blood cells in both control or stress conditions.

The researchers believe that regular blood donation is one type of activity that selects for mutations that allow cells to respond well to blood loss, but does not select the preleukaemic mutations associated with blood cancer.

Interactions of genes and the environment

Dominique Bonnet, Group Leader of the Haematopoietic Stem Cell Laboratory at the Crick, and senior author, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low levels of stress on blood cell production allow our blood stem cells to renew and we think this favours mutations that further promote stem cell growth rather than disease.

“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukaemic mutations and we will need to look at these results in much larger numbers of people. It might be that people who donate blood are more likely to be healthy if they’re eligible, and this is also reflected in their blood cell clones. But the insight it has given us into different populations of mutations and their effects is fascinating.”

Hector Huerga Encabo, postdoctoral fellow in the Haematopoietic Stem Cell Laboratory at the Crick, and first joint author with Darja Karpova from the DKFZ in Heidelberg, said: “We know more about preleukaemic mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to spot subtle genetic differences which might actually be beneficial in the long-term. We’re now aiming to work out how these different types of mutations play a role in developing leukaemia or not, and whether they can be targeted therapeutically.”

Source: The Francis Crick Institute

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The Truth About Bone Marrow Stem Cell Donation

On By ModernMedia
SAG Leukaemia. Credit: Scientific Animations CC0

While thousands of South Africans have registered as potential bone marrow stem cell donors, a critical challenge looms: donor attrition. These dropout rates, ranging from 23% to 56%, can significantly delay finding a suitable match for blood cancer patients in desperate need of a potentially life-saving transplant. This can unfortunately impact their chances of survival.

The good news is that donating stem cells is a safe and relatively simple process. With Bone Marrow Stem Cell Donation and Leukaemia Awareness Month taking place between 15 August and 15 October 2024, DKMS Africa aims to address some misconceptions that might deter registered donors from following through with donations.

Palesa Mokomele, Head of Community Engagement and Communications, unpacks these below:

Myth 1: Donating stem cells is a painful surgical procedure.

Fact: For over 90% of donors the process entails Peripheral Blood Stem Cell (PBSC) collection, a non-surgical procedure similar to donating blood. During PBSC, donors will rest comfortably while a needle is placed in each arm. Blood is drawn from one arm, passed through a machine that separates the stem cells, and the remaining blood is returned to the body through the other arm. While not painful, some donors may experience mild side effects like headaches, fatigue, or muscle aches, which typically resolve quickly.

For a small percentage of donors (around 2%), stem cells might be collected directly from the bone marrow in the pelvic bone. This minimally invasive procedure is performed under general anaesthesia. Although some donors experience temporary discomfort or soreness at the extraction site, the feeling is usually comparable to a bruise.

Myth 2: Donating takes too long and disrupts my life too much.

Fact: While the donation process involves some steps, it’s designed to be manageable. You’ll likely have a briefing call to explain the process, a health check to confirm your suitability, and an informative session about donation itself. The actual donation typically takes less than a day (4-6 hours) for the PBSC method.

For the bone marrow donation method, a hospital stay is involved, but it’s usually just three days. This includes check-in on day one, the procedure on day two, and discharge on day three.

Myth 3: Donating stem cells means missing a lot of work. 

Fact: The good news is that most donors can get back to work quickly. For PBSC donation, donors will likely be able to return within two days. If they donate bone marrow, a bit more recovery time is needed, so they should plan for about one week of leave.

Myth 4: My boss won’t be okay with me taking time off to donate.

Many employers are incredibly supportive of staff who donate stem cells. In our experience, most react positively to this selfless act. If your company doesn’t offer paid leave for donation, DKMS has a financial assistance programme that deals with lost wage compensation.

Myth 5: Donating stem cells will cost me money.

Fact: Donation is completely free of charge for the donor. DKMS covers all donation-related expenses, including travel, meals, and accommodation if needed. Financial support is also provided for a companion to join them at the hospital. The donor’s health insurance will never be involved, and DKMS handles the costs of any follow-up care that might be necessary.

“Seventeen-year-old Anele who was diagnosed with Acute Lymphoblastic Leukaemia (ALL), a type of cancer that affects the production of healthy blood cells, is just one of many patients in need of a stem cell transplant from a matching donor,” says Mokomele. “His father, Lawrence, is devastated, with his son now hanging on for dear life, waiting for that one person to be a match.”

“Every registered donor brings hope to a patient battling blood cancer. By staying committed to the cause, you help to ensure a readily available pool of potential matches, increasing a patient’s chance of receiving a transplant. Let’s give them a second chance at life!” she concludes.

Register today at https://www.dkms-africa.org/register-now

For more information, contact DKMS Africa on 0800 12 10 82.