(Press-News.org) Children treated for cancer with approaches such as chemotherapy can develop therapy-related myeloid neoplasms (a second type of cancer) with a dismal prognosis. Scientists at St. Jude Children's Research Hospital have characterized the genomic abnormalities of 84 such myeloid neoplasms, with potential implications for early interventions to stop the disease. A paper detailing the work was published today in Nature Communications.
The somatic (cancer) and germline (inherited) genomic alterations that drive therapy-related myeloid neoplasms in children have not been comprehensively described, until now. The researchers used a variety of sequencing techniques (whole exome, whole genome and RNA) to characterize the genomic profile of 84 pediatric therapy-related myeloid neoplasms. The data came from patients with leukemia, solid tumors or brain tumors who were treated with different types of chemotherapy and who all later developed myeloid neoplasms.
"One thing that we've known for a long time is once kids develop this secondary tumor, the outcome is really poor," said co-corresponding author Jeffery Klco, M.D., Ph.D., St. Jude Pathology. "The alterations that drive these tumors are different in children than they are in adults, underscoring the need to study these tumors specifically in pediatrics."
Collaboration yields new understanding
Results of the study revealed several notable mutations in the somatic setting, including changes in the Ras/MAPK pathway, alterations in RUNX1 or TP53, and rearrangements of KMT2A. Additionally, the results showed increased expression of a transcription factor called MECOM, which was associated with MECOM's abnormal proximity to an enhancer as a result of genetic rearrangements.
The research benefited from computational tools developed at St. Jude that are aimed at reducing error rates, including CleanDeepSeq and SequencErr. These approaches help to discriminate between true mutations and sequencing errors.
With these tools, the researchers could trace the mutations back as far as two years before a therapy-related myeloid neoplasm developed, when early interventions could potentially benefit patients.
"This work indicates that we can detect this type of malignancy early, to study if preventative therapies could benefit patients," said co-senior author Xiaotu Ma, Ph.D., St. Jude Computational Biology.
INFORMATION:
The study's other co-corresponding author is Tanja Gruber, Stanford University School of Medicine. Co-first authors are Jason Schwartz, Vanderbilt University Medical Center; Jing Ma, St. Jude; and Jennifer Kamens, Stanford University School of Medicine. Other St. Jude authors of the study are Tamara Westover, Michael Walsh, Samuel Brady, J. Robert Michael, Xiaolong Chen, Lindsey Montefiori, Guangchun Song, Gang Wu, Huiyn Wu, Ryan Hiltenbrand, Kim Nichols, Jamie Maciaszek, Yanling Liu, Priyadarshini Kumar, John Easton, Scott Newman, Jeffrey Rubnitz, Charles Mullighan, Stanley Pounds and Jinghui Zhang. Additional paper authors include Cristyn Branstetter, Arkansas Children's Northwest Hospital; and Michael Walsh, Memorial Sloan Kettering Cancer Center.
The research was funded in part by grants from the National Institutes of Health (1K08HL150282-01, P30CA021765, R01HL144653), Alex's Lemonade Stand Foundation, Burroughs Wellcome Fund, EvansMDS Foundation and ALSAC, the fundraising and awareness organization of St. Jude.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food -- because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at END
(Friday, February 12, 2021 - Toronto) -- Inhibiting a key enzyme that controls a large network of proteins important in cell division and growth paves the way for a new class of drugs that could stop glioblastoma, a deadly brain cancer, from growing.
Researchers at Princess Margaret Cancer Centre, the Hospital for Sick Children (SickKids) and University of Toronto, showed that chemically inhibiting the enzyme PRMT5 can suppress the growth of glioblastoma cells.
The inhibition of PRMT5 led to cell senescence, similar to what happens to cells during aging when cells lose the ability to divide and grow. Cellular senescence can also be a powerful tumour suppression mechanism, stopping ...
Space: the final frontier. What's stopping us from exploring it? Well, lots of things, but one of the major issues is space radiation, and the effects it can have on astronaut health during long voyages. A new review in the open-access journal END ...
Research over the last 20 years has shown that atherosclerosis is a chronic inflammatory condition of the arterial blood vessel wall. Soluble mediators such as cytokines and chemokines are pivotal players in this disease, promoting vascular inflammation. However, the development of anti-inflammatory therapeutics directed against such mediators that could prevent atherosclerosis has proven difficult, despite promising clinical studies in the recent past.
Previous anti-inflammatory therapeutic strategies to prevent atherosclerosis, heart attacks, strokes, rheumatoid arthritis and other inflammatory diseases have mainly been based ...
Remote sensing technology has become a vital tool for scientists over the past several decades for monitoring changes in land use, ice cover, and vegetation across the globe. Satellite imagery, however, is typically available at only coarse resolutions, allowing only for the analysis of broad trends over large areas. Remote-controlled drones are an increasingly affordable alternative for researchers working at finer scales in ecology and agriculture, but the laser-based technology used to estimate plant productivity and biomass, such as light detection and ranging (LiDAR), remain prohibitively expensive.
In research presented in a recently published issue of Applications in Plant Sciences, researchers ...
New research has shown that results of blood tests routinely performed by GPs everywhere contain a hidden fingerprint that can identify people silently developing potentially fatal liver cirrhosis.
The researchers have developed an algorithm to detect this fingerprint that could be freely installed on any clinical computer, making this a low-cost way for GPs to carry out large scale screening using patient data they already hold.
Liver cirrhosis is the second leading disease causing premature death in working-age people (after heart disease). It develops silently ...
Peer-reviewed / Observational study / People
For the study, published in the journal Diabetes, Obesity and Metabolism, researchers analysed data from the UK Biobank of 500,000 people aged 58 years on average, and found that people with higher than normal blood sugar levels were 42% more likely to experience cognitive decline over an average of four years, and were 54% more likely to develop vascular dementia over an average of eight years (although absolute rates of both cognitive decline and dementia were low).
The associations remained true after other influential factors had been taken into account - including age, deprivation, smoking, BMI and whether or not participants had cardiovascular disease.
People with ...
A team of scientists have measured the relative importance of the different obstacles that carbon dioxide (CO2) encounters in its voyage from the atmosphere to the interior of plant cells, where it is converted into sugars. This research leading method provides much needed information that will help to increase the yield of important food crops such as cowpea, soybean and cassava.
"Our data highlights promising targets to improve the diffusion of CO2 through the leaf with the aim of boosting crop productivity," says lead author Dr Tory Clarke, who works at The Australian National University (ANU), as part of the Realizing Increased Photosynthetic ...
Psychologists at the University of Bath, Cardiff, and London have developed the first ever 'mind-reading questionnaire' to assess how well people understand what others are really thinking.
A new approach to 'mind-reading' has been developed by researchers at the University of Bath, Cardiff, and London to improve how well we understand what others are thinking. And it transpires that women are much better than men at putting themselves in someone else's shoes.
Mind-reading, sometimes referred to in psychology as 'mentalising', is an important ability enabling us to pick-up on subtle behavioural cues that might indicate that someone we are speaking to is thinking ...
A new modelling study published in Anaesthesia (a journal of the Association of Anaesthetists) shows that the UK's coronavirus vaccination program is already reducing daily deaths. However, reductions of hospital and intensive care (ICU) admissions will likely take several weeks longer, with large reductions seen by the end of March and continuing into April.
The study is by Professor Tim Cook (Consultant in Anaesthesia and Intensive Care Medicine, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK, and Honorary Professor, School of Medicine, University of Bristol, UK) and Mr ...
Anti-retroviral drugs are a vital tool in the prevention and treatment of HIV. A new study of pregnant women in Tanzania shows that life-long antiviral treatment also seems to prevent viral transmission from mother to baby. The results of the study, which was conducted in part by researchers at Karolinska Institutet in Sweden and published in Lancet HIV, make a promising contribution to the WHO's work with HIV prevention in low and middle-income countries.
Just over eight years ago, the World Health Organisation (WHO) issued recommendations known as Option B+ for a simpler and more effective prevention and treatment for HIV during and beyond pregnancy in low and middle-income countries.
One arm of the Option B+ programme involved ensuring that pregnant women with HIV ...
