PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

New Sylvester cancer study provides insight into underlying gene mutations in myelodysplastic syndromes

Findings could lead to development of more effective drug combinations to treat MDS patients

2023-12-09
(Press-News.org) EMBARGOED UNTIL DECEMBER 9, 2023, AT 12:45 P.M. ET

A new study from researchers with Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and collaborating organizations provides insight into the underlying mechanisms of gene mutations commonly seen in patients with myelodysplastic syndromes (MDS) and other myeloid neoplasms.

Their findings, to be presented at ASH 2023, the American Society of Hematology’s annual meeting in Santa Diego, Dec. 9-12, could lead to development of more effective drug combinations and targeted therapies for MDS patients carrying these mutations.

Background

About half of MDS patients carry genetic alterations, also known as somatic mutations, in the spliceosome genes, with SF3B1 being the most common one. However, no successful therapy exists to target this pathway.

Previous findings from a phase 2 clinical trial of selinexor, an Exportin-1 (XPO1) inhibitor for relapsed or refractory MDS, showed increased effectiveness in patients with SF3B1-mutated MDS. Exportin-1 is the nuclear export receptor responsible for exporting more than 200 proteins, but also plays a role in transporting multiple small nuclear RNAs and select messenger RNAs.

Sylvester researchers and collaborators hypothesized that 1) inhibiting XPO1 may preferentially affect SF3B1-mutant cells via altered splicing and 2) high-risk MDS patients with this mutation would have a better response to dose-controlled, targeted drug combinations with next-generation XPO1 inhibitors.

Methodology

For this study, the researchers deployed a combination of scientific techniques in their analysis, including:

RNA sequencing to evaluate the underlying mechanism for the SF3B1 mutation’s sensitivity to XPO1 inhibitors. Whole genome CRISPR screens in two myeloid leukemia cell lines with eltanexor, a next-generation XPO1 inhibitor with lower toxicity than the drug selinexor. The analyses identified several novel targets that were tested for synergy in combination with eltanexor for the specific SF3B1 mutation. Two drugs were identified for strong synergy with eltanexor: venetoclax and navitoclax. In vitro studies to test combinations identified from the CRISPR screen using cell viability tests and western blots. In vivo studies to further validate these combinations through use of transplant tests in laboratory mice. Expert Commentary

“This is the first study to examine the effects of XPO1 inhibition on RNA export to better understand the underlying mechanisms involved with the most common mutation seen in MDS patients,” explained Sana Chaudhry, Sylvester researcher and lead presenter at the ASH conference.

“Our study’s findings may contribute to development of synergistic therapeutic combinations to better treat SF3B1-mutant MDS,” said Justin Taylor, M.D., senior author and a member of the Translational and Clinical Oncology Program at Sylvester.

Additionally, Taylor noted, recent data from human studies has shown that venetoclax can overcome the poor prognosis often associated with acute myeloid leukemia patients with mutations. “As a result, combining eltanexor with venetoclax could represent a potentially effective SF3B1-specific therapy,” he concluded.

_ _ _

Disclosures

The authors had no relevant conflicts of interest to declare.

# # #

Presentation Title:

44 “Altered RNA Export in SF3B1 Mutants Increases Sensitivity to Nuclear Export Inhibition”

Presentation Date/Time:

Saturday, Dec. 9, 2023, 9:45 am

 

 

END



ELSE PRESS RELEASES FROM THIS DATE:

First-in-human clinical trial of CAR T cell therapy with new binding mechanism shows promising early responses

2023-12-09
SAN DIEGO – Early results from a Phase I clinical trial of AT101, a new CAR T cell therapy that uses a distinct binding mechanism to target CD19, show a 100 percent complete response (CR) rate at the higher dose levels studied in the trial, according to researchers from the University of Pennsylvania Perelman School of Medicine and Penn Medicine’s Abramson Cancer Center. The findings were published today in Molecular Cancer and presented at the 65th American Society of Hematology (ASH) Annual Meeting ...

Long-term results show combination treatment that skips chemotherapy is effective for older patients with Ph+ ALL

2023-12-09
Older patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who were not good candidates for the standard treatment of intensive chemotherapy had a median overall survival (OS) of 6.5 years on an alternate regimen of dasatinib and blinatumomab.  These long-term results from the S1318 clinical trial will be presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego on December 9 (abstract 1499). Anjali S. Advani, MD, a SWOG investigator at Cleveland Clinic Cancer Institute, led the study, with ...

Mindfulness could help women with opioid use disorder better control drug urges

2023-12-09
Mindfulness-Oriented Recovery Enhancement (MORE) — a behavioral intervention that integrates training in mindfulness, emotion regulation strategies and savoring of natural rewards — could hold the key to mitigating relapse in women undergoing medically assisted opioid use disorder treatment, a Rutgers study found.   The pilot study published in the journal Explore, is the first to evaluate the potential neural changes that underlie women’s emotion regulation and craving after an eight-week MORE intervention.   Previous studies have shown that women report higher opioid craving and show a greater inability to ...

TTUHSC’s ARPA-H membership will spur innovation, improve access for West Texas patients

TTUHSC’s ARPA-H membership will spur innovation, improve access for West Texas patients
2023-12-09
Imagine if scientists developed a customizable cancer vaccine that was available — and affordable — for everyone. What if a patient scheduled for surgery also had the option of taking a pill whose composition includes nanorobotics capable of performing the procedure? These and other medical scenarios may seem far-fetched and better suited to a science fiction thriller. However, the Advanced Research Projects Agency for Health (ARPA-H) is seeking to take such ideas from the drawing board to ...

Global annual finance flows of $7 trillion fueling climate, biodiversity, and land degradation crises

2023-12-09
Almost US$7 trillion per year in government subsidies and private investment - around 7 per cent of global GDP - has a direct negative impact on nature. Nature-based solutions remain dramatically underfunded. Current public and private finance flows are only US$200 billion per year. To meet climate, biodiversity, and restoration targets, this needs to triple by 2030 and quadruple by 2050. Realignment of public and private nature-negative finance flows is urgently needed Dubai, 9 December 2022 – Close to $7 trillion is invested globally each year in activities that have a direct negative impact on nature from both public and private sector sources - equivalent to ...

Tracing how the infant brain responds to touch with near-infrared spectroscopy

Tracing how the infant brain responds to touch with near-infrared spectroscopy
2023-12-09
Tokyo, Japan – Researchers from Tokyo Metropolitan University have measured how oxygenated hemoglobin levels in the blood change in infants’ brains in response to touch. Using spectroscopy methods with external sensors placed on the scalp of sleeping infants, they found that the time at which levels peak doesn’t change with infant age, but the amount by which it varies over time does. Insights like this shed light on how the physiology of infants develop. The first phase of a newborn’s life is a dazzling array of rapid developmental ...

These are the world's most effective charities

2023-12-09
Which charities will be most effective in ensuring your donation is put to good use? For the first time in the Netherlands, researchers applied scientific methods to pinpoint which charities achieve the most with the donations they receive. The University of Amsterdam and Stichting Doneer Effectief (Donate Effectively Foundation) unveiled the list on Friday, 8 December, during a sold out evening in Rotterdam. ‘We are talking about the Champions League of good causes,’ says professor of Philanthropy & Sustainable Investment Paul Smeets of the University of Amsterdam. The ranking ...

When is an aurora not an aurora?

When is an aurora not an aurora?
2023-12-08
The shimmering green, red and purple curtains of the northern and southern lights — the auroras — may be the best-known phenomena lighting up the nighttime sky, but the most mysterious are the mauve and white streaks called Steve and their frequent companion, a glowing green "picket fence." First recognized in 2018 as distinct from the common auroras, Steve — a tongue-in-cheek reference to the benign name given a scary hedge in a 2006 children's movie — and its associated picket fence were nevertheless thought to be caused by the same physical processes. But scientists were left scratching their heads about how these glowing emissions ...

Advisory panel issues field-defining recommendations for US government investments in particle physics research

2023-12-08
The High Energy Physics Advisory Panel (HEPAP) to the High Energy Physics program of the Office of Science of the U.S. Department of Energy and the National Science Foundation’s Division of Physics has released a new Particle Physics Project Prioritization Panel (P5) report, which outlines particle physicists’ recommendations for research priorities in a field whose projects — such as building new accelerator facilities — can take years or decades, contributions from thousands of scientists, and billions of dollars.  The 2023 P5 report represents the major activity in the field of particle physics that ...

Doctors discover many patients at UNC’s Inflammatory Bowel Disease Clinic screen positive for malnutrition

Doctors discover many patients at UNC’s Inflammatory Bowel Disease Clinic screen positive for malnutrition
2023-12-08
CHAPEL HILL, NC — Eating food and absorbing its nutrients is an everyday occurrence, but this normal activity can look different for someone who suffers from inflammatory bowel disease. IBD, which includes Crohn’s disease and ulcerative colitis, can cause chronic inflammation of the digestive tract – which for many reasons can lead to malnutrition. This malnourished state is associated with an increased risk of morbidity and mortality, and new findings show that many patients in IBD clinic screen positive for malnutrition, leading to the critical need for same-day ...

LAST 30 PRESS RELEASES:

Scientists put forth a smarter way to protect a smarter grid

An evolutionary mystery 125 million years in the making

Data science approach to identifying thermal conductivity-related structural factors in amorphous materials

Deciphering the male breast cancer genome

Detection of suicide-related emergencies among children using real-world clinical data: A free webinar from the Brain & Behavior Research Foundation

Editor-in-Chief of Sustainability and Climate Change Madhavi Venkatesan named USA TODAY Woman of the Year for Massachusetts for leading plastic bottle ban efforts

Tests show high-temperature superconducting magnets are ready for fusion

Zika vaccine safe, effective when administered during pregnancy

Firearm ownership is correlated with elevated lead levels in children, study finds

Role of African women and young people in agricultural service provision investigated in new CABI-led study

26th International Conference of the Redox Medicine Society Set for June 2024 in Paris, France

Geologists explore the hidden history of Colorado’s Spanish Peaks

Webb unlocks secrets of one of the most distant galaxies ever seen

3D-printed skin closes wounds and contains hair follicle precursors

Discovered a RNA molecule that helps prevent DNA replication errors

Small and overlooked: Amount of repetitive DNA in blood hints at cancer early

Study determines the original orientations of rocks drilled on Mars

Illinois study: Supporting disease-challenged broiler chickens through nutrition

Communities severed by roads and traffic experience a larger number of collisions in New York City

Study shows new class of antivirals that works against SARS-CoV-2

Cost of direct air carbon capture to remain higher than hoped

Unraveling the mystery of chiton visual systems

Case Western Reserve University-led research team discovers new method to test for oral cancer

Firearm access and gun violence exposure are common in Black and native communities

New AI smartphone tool accurately diagnoses ear infections

Screen time and parent-child talk when children are ages 12 to 36 months

Firearm access and gun violence exposure among American Indian or Alaska native and Black adults

Associations of medical debt with health status, premature death, and mortality in the US

Low-cost liquid tames tooth decay

More than 1/3 illicit drugs sold on the dark web contain unexpected substances

[Press-News.org] New Sylvester cancer study provides insight into underlying gene mutations in myelodysplastic syndromes
Findings could lead to development of more effective drug combinations to treat MDS patients