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

New genetic finding uncovers hidden cause of arsenic resistance in acute promyelocytic leukemia

Point mutation in healthy PML gene thwarts arsenic trioxide’s attack on leukemia cells

2025-07-04
(Press-News.org)

Researchers at Zhejiang University School of Medicine have identified a single point mutation in the normal PML gene that can block the effect of arsenic trioxide, a frontline drug for acute promyelocytic leukemia. This discovery uncovers a hidden cause of treatment failure and suggests a new target for genetic screening in relapsed patients. This work addresses the urgent issue of why some patients relapse despite a therapy that otherwise greatly improves survival.

Mutation Explains Why a Small Portion of Leukemia Patients Relapse on Arsenic Therapy

Arsenic trioxide cures most acute promyelocytic leukemia patients, but some patients relapse without an apparent genetic reason. Discovering that mutations in the intact PML allele confer resistance offers a way to predict and prevent treatment failure. Clinicians could add this test to standard panels to guide personalized therapy. For diagnostic developers, it points to the development of new assays. Healthcare policymakers can update screening guidelines to reduce relapse costs and improve patient outcomes. The finding also advances scientific understanding of how normal and fusion proteins interact under treatment.

“We have long been puzzled by why a small subset of patients still relapse despite arsenic trioxide’s proven efficacy,” says Prof. Hua Naranmandura. “This study finally uncovers a hidden genetic factor, bringing us closer to preventing those relapses.”

A216V Change in Healthy PML Locks On Fusion Protein, Revealing New Drug-Resistance Switch

The researchers identified an A216V mutation in the unrearranged PML gene of a relapsed patient, while the PML::RARα fusion gene remained unmutated. Cells carrying this mutation failed to degrade the disease-driving fusion protein when treated with arsenic trioxide, indicating resistance to the treatment. Laboratory models demonstrated that the mutant PML binds more tightly to the PML::RARα protein, thereby preventing the drug-induced destabilization of this complex. Importantly, deleting the coiled-coil region of the mutant PML abolished this abnormal interaction and restored drug sensitivity, pinpointing a mechanism for resistance and a possible intervention point.

Patient Sequencing and Engineered Cells Spotlight How Mutant PML Thwarts Arsenic-Induced Breakdown

The team sequenced bothPML and PML::RARα genes from patient samples and compared the arsenic sensitivity of PML::RARα fusion protein to those in standard cell lines. They then engineered laboratory cells to carry either the standard or mutant versions of PML, treated them with arsenic trioxide, and used protein assays and high-resolution microscopy to track the effects of the drug on the leukemia-driving fusion protein. This combination of patient data and controlled cell experiments ensured robust, clinically relevant results.

“We hope that adding unrearranged PML screening into standard panels will become routine,” says Prof. Hua Naranmandura. “Early identification of at-risk patients means we can tailor therapy before resistance emerges, ultimately improving survival and reducing costs.”

Published in Research in May 2025, this study shows that testing the unrearranged PML allele is crucial for understanding and overcoming arsenic trioxide resistance in acute promyelocytic leukemia. Incorporating screening for such mutations into clinical practice could lead to more effective and more personalized treatment strategies for patients at risk of relapse.

Sources: https://doi.org/10.34133/research.0696

END



ELSE PRESS RELEASES FROM THIS DATE:

Native habitats hold the key to the much-loved smashed avocado’s future

2025-07-04
The future of smashed avocado might depend on patches of native vegetation preserved alongside farmland, as new Curtin research reveals the hidden role of these habitats in supporting the insects that keep crops - and brunch menus - thriving. The research, published this week, found that insect communities in avocado orchards adjacent to native remnant vegetation foraged on more than twice as many plant species at times when crop flowering was limited, compared to those in orchards bordered by pasture. Insects with more diverse food sources are more likely to survive and pollinate crops so this finding offers a potential clue to safeguarding ...

Using lightning to make ammonia out of thin air

2025-07-04
University of Sydney researchers have harnessed human-made lightning to develop a more efficient method of generating ammonia – one of the world’s most important chemicals. Ammonia is also the main ingredient of fertilisers that account for almost half of all global food production. The team have successfully developed a more straightforward method to produce ammonia (NH3) in gas form. Previous efforts by other laboratories produced ammonia in a solution (ammonium, NH4+), which requires more energy and processes to transform it into the final gas product. The current method to generate ammonia, the Haber-Bosch process, comes at great ...

Machine learning potential-driven insights into pH-dependent CO₂ reduction

2025-07-04
Some of the most encouraging results for reaction-enhancing catalysts come from one material in particular: tin (Sn). While Sn's overall utility as a catalyst is well-known, its underlying structure-performance relationship is poorly understood, which limits our ability to maximize its potential. To address this knowledge gap, researchers at Tohoku University's Advanced Institute for Materials Research (WPI-AIMR) used machine learning to characterize Sn catalyst activity. The highly accurate simulations could be a game-changer that helps researchers swiftly and simply ...

Physician associates provide safe care for diagnosed patients when directly supervised by a doctor

2025-07-03
Physician associates provide safe and effective care when they work under the direct supervision of doctors and care for patients who have already been diagnosed, or when they undertake procedures for which they have been highly trained, finds a rapid review published in The BMJ today. However, the rapid review on the safety and effectiveness of physician associates found insufficient evidence to support them assessing undiagnosed patients under indirect supervision—when seeing undiagnosed patients in primary care, for example. Patient satisfaction levels ...

How game-play with robots can bring out their human side

2025-07-03
The more we interact with robots, the more human we perceive them to become – according to new research from the University of East Anglia. It may sound like a scene from Blade Runner, but psychologists have been investigating exactly what makes robot interactions feel more human. A new paper published today reveals that playing games with robots to ‘break the ice’ can help bring out their human side. The research team say that the implications are significant for the future of robotics. As robots take on roles from care-giving to customer service, designing interactions that promote social engagement ...

Asthma: patient expectations influence the course of the disease

2025-07-03
Individual expectations about one's health can influence him/her future condition and the speed of the progression of a disease: in fact, a research conducted by researchers of psychology at the Università Cattolica del Sacro Cuore, Milan campus, shows that, after a diagnosis of asthma, people who are optimistic about their health will have a slower progression of the disease. The study was published in the journal Health Expectations (Wiley) and conducted by full Professor Francesco Pagnini of the Department of Psychology at the Università Cattolica and colleagues. Professor Pagnini explains: “this study was developed in response to ...

UNM physician tests drug that causes nerve tissue to emit light, enabling faster, safer surgery

2025-07-03
When surgeons dissect tissue to remove a tumor or make a repair they must work cautiously, relying on electrophysical monitors and their own anatomical knowledge to avoid cutting nerves, which could complicate the patient’s recovery. A University of New Mexico surgeon has helped develop and test a first-of-its-kind drug that binds to nerve tissue and fluoresces – emits light – enabling surgeons to better see the nerves they’re trying to work around. A newly published study in Nature Communications ...

New study identifies EMP1 as a key driver of pancreatic cancer progression and poor prognosis

2025-07-03
The latest research published in Genes & Diseases unveils groundbreaking insights into the role of the aging process and the associated factor EMP1 in the progression of resectable pancreatic cancer (PC). The study, conducted by a team of researchers from the University of Chinese Academy of Sciences and Chongqing Medical University, has established a prognostic model that links EMP1 expression with adverse clinical outcomes, particularly among older PC patients.   Pancreatic cancer remains a highly aggressive ...

XPR1 identified as a key regulator of ovarian cancer growth through autophagy and immune evasion

2025-07-03
  A recent study published in Genes & Diseases reveals a novel role of XPR1 in promoting ovarian cancer growth by regulating autophagy and MHC-I expression. The research, conducted by scientists from Chongqing Medical University, identifies XPR1 as a critical factor influencing the aggressiveness of ovarian cancer through its interaction with LAMP1 and the PI3K/Akt/mTOR signaling pathway. These findings shed light on new therapeutic targets for ovarian cancer, a malignancy known for its poor prognosis and resistance to immune checkpoint inhibitors.   The ...

Flexible, eco-friendly electronic plastic for wearable tech, sensors

2025-07-03
CLEVELAND—Researchers at Case Western Reserve University have developed an environmentally safer type of plastic that can be used for wearable electronics, sensors and other electrical applications. The material, a so-called ferroelectric polymer, is made without fluorine, considered a “forever” chemical that hurts the environment because compounds made with it don’t break down quickly or at all. Although the researchers are still working to improve the material’s electric and elastic properties, the potential is vast for its flexibility of electronic uses and eco-friendly structure. “How this material ...

LAST 30 PRESS RELEASES:

Unlocking the hidden biodiversity of Europe’s villages

Planned hydrogen refuelling stations may lead to millions of euros in yearly losses

Planned C-sections increase the risk of certain childhood cancers

Adults who have survived childhood cancer are at increased risk of severe COVID-19

Drones reveal extreme coral mortality after bleaching

New genetic finding uncovers hidden cause of arsenic resistance in acute promyelocytic leukemia

Native habitats hold the key to the much-loved smashed avocado’s future

Using lightning to make ammonia out of thin air

Machine learning potential-driven insights into pH-dependent CO₂ reduction

Physician associates provide safe care for diagnosed patients when directly supervised by a doctor

How game-play with robots can bring out their human side

Asthma: patient expectations influence the course of the disease

UNM physician tests drug that causes nerve tissue to emit light, enabling faster, safer surgery

New study identifies EMP1 as a key driver of pancreatic cancer progression and poor prognosis

XPR1 identified as a key regulator of ovarian cancer growth through autophagy and immune evasion

Flexible, eco-friendly electronic plastic for wearable tech, sensors

Can the Large Hadron Collider snap string theory?

Stuckeman professor’s new book explores ‘socially sustainable’ architecture

Synthetic DNA nanoparticles for gene therapy

New model to find treatments for an aggressive blood cancer

Special issue of Journal of Intensive Medicine analyzes non-invasive respiratory support

T cells take aim at Chikungunya virus

Gantangqing site in southwest China yields 300,000-year-old wooden tools

Forests can’t keep up: Adaptation will lag behind climate change

Sturgeon reintroduction initiative yields promising first-year survival rate

Study: Babies’ poor vision may help organize visual brain pathways

Research reveals Arctic region was permafrost-free when global temperatures were 4.5˚ C higher than today

Novel insights into chromophobe renal cell carcinoma biology and potential therapeutic strategies

A breakthrough in motor safety: AI-powered warning system enhances capability to uncover hidden winding faults

Research teases apart competing transcription organization models

[Press-News.org] New genetic finding uncovers hidden cause of arsenic resistance in acute promyelocytic leukemia
Point mutation in healthy PML gene thwarts arsenic trioxide’s attack on leukemia cells