A new editorial paper was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “AGO2 in T-prolymphocytic leukemia: its canonical and noncanonical deregulation and function.”

In their new editorial, researchers Till Braun, Hanna Klepzig and Marco Herling from University of Cologne and University of Leipzig T-prolymphocytic leukemia (T-PLL) — a mature T-cell neoplasm with an aggressive and treatment refractory course. 

“In light of limited therapeutic options median overall survival times from diagnosis is hardly longer than 2 years.” 

There is currently no FDA- or EMA-approved drug for the treatment of T-PLL. Although 80–90% of patients experience a response to the most efficient single agent Alemtuzumab, relapses are common within the first 12–24 months following this first-line treatment. One of the defining characteristics of T-PLL is the presence of the chromosomal aberrations inv(14) or t(14;14), which lead to constitutive expression of the proto-oncogene T-cell leukemia 1A (TCL1A). 

This adapter molecule is centrally implicated in the enhanced T-cell receptor (TCR) signaling that is observed in the memorytype malignant T-cell. Other recurrent genomic alterations that have been identified in T-PLL affect the genes ataxia telangiectasia mutated (ATM), Janus kinase (JAK), signal transducer and activator of transcription (STAT), and MYC. In a recent study published by Braun et al., the team made significant advances in the understanding of the biology of T-PLL at the level of post-transcriptional gene regulation. 

“For the first time, descriptive and mechanistic data implicated the involvement of molecules of the RNA interference (RNAi) machinery in T-PLL’s leukemogenesis and by that refined our current disease model by concepts beyond protein-coding genes.”

DOI - https://doi.org/10.18632/oncotarget.28378

Correspondence to - Marco Herling - marco.herling@medizin.uni-leipzig.de

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Keywords - cancer, leukemia, T-PLL, AGO2, microRNA

About Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Oncotarget

AGO2 in T-prolymphocytic Leukemia (T-PLL)

While researchers work to improve lobular breast cancer screening, innovative treatments are improving outcomes for patients with a condition diagnosed in more than 40,000 Americans each year.

Ohio State medical oncologist Arya Roy, MD, shares details about lobular breast cancer, also called invasive lobular carcinoma (ILC), including risks, symptoms and treatments.

Episode 198: What you need to know about lobular breast cancer, with Arya Roy, MD

BUFFALO, NY – October 20, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 16, 2025, titled “Widespread folate receptor expression in pediatric and adolescent solid tumors – opportunity for intraoperative visualization with the novel fluorescent agent pafolacianine.”

In this study, led by first author Ashley C. Dodd from Ann & Robert H. Lurie Children’s Hospital and corresponding author Timothy B. Lautz from the same institution and Northwestern University Feinberg School of Medicine, researchers discovered that folate receptor beta (FRβ) is widely expressed in various pediatric and adolescent solid tumors. This finding highlights FRβ as a promising target for improving the accuracy of tumor surgery using a fluorescent imaging agent known as pafolacianine.

Pediatric cancers are often challenging to remove completely during surgery, particularly when tumors spread or form small metastases. Fluorescence-guided surgery is a method that helps surgeons better identify tumors during operations using special imaging dyes. However, commonly used dyes such as indocyanine green are not tumor-specific and rely on general features of blood vessel permeability, limiting their precision.

In this study, researchers investigated the potential of pafolacianine, a next-generation dye that targets folate receptors, for pediatric use. Folate receptors are proteins commonly found on the surface of cancer cells. Pafolacianine is already FDA-approved for adults with ovarian and lung cancers due to its ability to bind these receptors and highlight tumors during surgery. 

The research team analyzed tissue samples from 13 young patients diagnosed with various cancers, including Wilms tumor, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, Ewing sarcoma, and neuroblastoma. The results showed that FRα was predominantly absent, whereas FRβ was present in 100% of the tumor samples. Notably, FRβ appeared both on the tumor cells and in the surrounding tumor microenvironment but showed little to no expression in normal tissue, making it an excellent candidate for targeted imaging.

“In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors.”

This consistent expression of FRβ in pediatric tumors is a significant and novel finding. Earlier studies primarily linked FRβ to immune cells called tumor-associated macrophages. This study reveals that FRβ is also expressed directly on tumor tissue, which could help surgeons better distinguish cancer from healthy tissue during procedures.

Based on these results, the team has launched a clinical trial to evaluate pafolacianine in children undergoing surgery for metastatic lung tumors. If successful, this method could make pediatric cancer surgery safer and more effective.

Overall, this study suggests that targeting FRβ with pafolacianine could serve as a tumor-agnostic imaging strategy, applicable across a wide range of pediatric solid tumors. This represents a potential advancement in real-time surgical imaging and a step forward in pediatric cancer care.

DOI - https://doi.org/10.18632/oncotarget.28772

Correspondence to - Timothy B. Lautz - TLautz@luriechildrens.org

Abstract video - https://www.youtube.com/watch?v=0its0QkOcwM

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Folate Receptor Beta Found in Pediatric Tumors May Improve Fluorescence-Guided Cancer Surgery

Loretta Ross is a public intellectual, professor, activist, and author of Calling In, a collection of stories from five remarkable decades working in social justice movements, including reproductive justice, white supremacy, and women of color organizing. Loretta and Leader’s Way host Brandon Nappi go deep into conversation about why calling people in—inviting them into conversation instead of conflict by focusing on your shared values over a desire for punishment—is a powerful and strategic choice toward making real change.

Host: Brandon Nappi
Guest: Loretta Ross

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68: A World Thirsty for Accountability with Loretta Ross

BUFFALO, NY — October 21, 2025 — A new #editorial was #published in Aging-US on October 13, 2025, titled “Longevity clinics: between promise and peril.”

In this editorial, Marco Demaria, Editor-in-Chief of Aging-US, from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), reviews the rapid rise of longevity clinics worldwide. 

Longevity clinics have emerged globally in response to increasing demand for personalized, preventive healthcare. Located in countries such as the United States, Switzerland, and the United Arab Emirates, these centers offer advanced diagnostic services, including genomic testing, advanced imaging, and multi-omics profiling. Their goal is to extend healthspan—the number of years a person lives in good health—through customized lifestyle interventions, nutritional guidance, and, in some cases, experimental therapies.

“Longevity clinics embody an important vision: healthcare is personalized, preventive, and engaged.”

Although the concept of proactive aging care is attractive, the editorial raises serious concerns about the scientific and ethical foundations of these clinics. Many operate outside conventional medical systems and lack connections to academic geroscience. This disconnection allows them to market expensive interventions without sufficient clinical validation. Program costs can range from €10,000 to over €100,000 per year, limiting access to wealthy individuals while leaving out populations most at risk for premature aging.

Despite these challenges, Dr. Demaria notes that longevity clinics may contribute meaningfully to innovation. By collecting extensive, long-term health data from clients, these clinics have the potential to identify early biomarkers of aging and detect signs of age-related diseases. Unlike traditional clinical trials, which are limited in scope and duration, longevity clinics track a wide range of health data over time. When paired with artificial intelligence tools, this information could help advance the science of healthy aging.

However, several risks remain. Many clinics lack standardized protocols, and the tools they use, such as biological age calculators or hormone therapies, often lack accuracy or clear clinical value. Without proper guidelines, clients may receive advice that is confusing or not scientifically supported. This can reduce public trust in the broader field of longevity research.

To ensure these clinics contribute positively to health innovation, the editorial outlines different key steps: greater collaboration with academic researchers, the adoption of standardized protocols, increased transparency, and work toward regulatory clarity. Broader access must also be considered by developing scalable and more affordable models, possibly through partnerships with public health systems.

Ultimately, longevity clinics represent both a major opportunity and a serious concern. If integrated responsibly with science, policy, and public health, they could support a shift toward personalized, preventive healthcare. Without this alignment, however, they risk reinforcing inequality and weakening the credibility of the science behind aging.

DOI - https://doi.org/10.18632/aging.206330

Corresponding author - Marco Demaria — m.demaria@umcg.nl

Abstract video - https://www.youtube.com/watch?v=Bt84xBdii0s

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Aging-US

The Rise of Longevity Clinics: Promise, Risk, and the Future of Aging

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare blood cancer that primarily affects older adults. One of the key challenges in diagnosing and treating BPDCN is that it closely resembles other forms of leukemia in both appearance and behavior. This overlap often leads to delays or uncertainty in diagnosis, especially since currently there is no single, reliable marker that clearly distinguishes BPDCN from related diseases.

To address this issue, researchers from the City of Hope Comprehensive Cancer Center investigated the genetic profile of BPDCN.  Their study, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience,” was published in Oncotarget (Volume 16).

Full blog - https://www.oncotarget.org/2025/10/22/genetic-study-identifies-potential-diagnostic-marker-for-rare-blood-cancer-bpdcn/

Paper DOI - https://doi.org/10.18632/oncotarget.28742

Correspondence to - Michelle Afkhami - mafkhami@coh.org

Abstract video - https://www.youtube.com/watch?v=wUjr3uU3onI

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Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50

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Genetic Study Identifies Potential Diagnostic Marker for Rare Blood Cancer BPDCN

In this episode, Ji Li discusses her book, At the Frontier of God’s Empire with Chloë Starr. The book tells the story of French missionary Alfred Caubrière who before his murder in 1948 left behind some 800 letters to his family, as well as 13 volumes of transcripts of everyday conversations in the local dialect among villagers in Santaizi, Manchuria. The episode discusses the life of Caubrière and especially his experience of the weeks-long siege of Santaizi church by the Boxer Rebels in 1900, as well as his depictions of the lives and beliefs of local Catholics.

Ji Li,  At the Frontier of God’s Empire: A Missionary Odyssey in Modern China

BUFFALO, NY — October 23, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 11, 2025, titled “Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice.”

In this study led by first author Takashi Ohira and corresponding author Hiroshi Kaji from Kindai University Faculty of Medicine, researchers found that female mice lacking the gene for plasminogen activator inhibitor-1 (PAI-1) were protected from age-related muscle weakness and bone thinning. This suggests that PAI-1 could be a potential target for future treatments to reduce frailty in aging populations.

As the global population continues to age, more people are affected by conditions such as sarcopenia and osteoporosis. These disorders involve the progressive loss of skeletal muscle mass and bone density, leading to reduced mobility, a greater risk of falls, and a lower quality of life.

To investigate the role of PAI-1 in aging, researchers compared young (6-month-old) and aged (24-month-old) male and female mice, with and without the PAI-1 gene. They found that PAI-1 levels increased with age in both sexes. However, only female mice lacking the PAI-1 gene experienced a significant reduction in age-related muscle and bone loss.

Female mice without PAI-1 maintained stronger grip strength and greater muscle mass in their lower limbs. They also showed less cortical bone loss in their femurs and tibias. In contrast, male mice did not experience the same benefits, despite also showing increased levels of PAI-1 with age. These results suggest that PAI-1 contributes to aging-related decline in a sex-specific manner.

“The present study found that lower limb muscle mass, gastrocnemius and soleus muscle tissue weights, and grip strength were significantly lower in 24-month-old male and female wild-type mice than in their 6-month-old counterparts.”

PAI-1 plays key roles in blood clotting, inflammation, and cellular senescence—a process in which aging cells release harmful molecules that affect nearby tissues. One of these molecules, interleukin-6 (IL-6), is a major driver of inflammation. The researchers found that aged female mice lacking PAI-1 had lower IL-6 levels in both muscle and blood, suggesting that PAI-1 may contribute to muscle and bone loss by promoting inflammation. These protective effects were also not associated with changes in muscle protein turnover or reductions in fibrous tissue, reinforcing the idea that PAI-1’s impact is likely driven by inflammatory signaling.

This study highlights PAI-1 as a promising therapeutic target for slowing or preventing age-related declines in muscle and bone health, particularly in women. Since postmenopausal women are especially vulnerable to osteoporosis and frailty, a better understanding of how PAI-1 contributes to aging could lead to new strategies for maintaining strength and mobility in later life. Further research is needed to explore how PAI-1 interacts with other age-related biological changes and why its effects differ between sexes.

DOI - https://doi.org/10.18632/aging.206318

Corresponding author - Hiroshi Kaji - hkaji@med.kindai.ac.jp

Abstract video - https://www.youtube.com/watch?v=hg4qKf-oO2I

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PAI-1 Deficiency Protects Aging Female Mice from Muscle and Bone Loss

In this special episode of the Yale University Press podcast, Jennifer Banks, Senior Executive Editor in Religion and the Humanities, talks with Anthony T. Kronman about his latest book, True Conservatism: Reclaiming Our Humanity in an Arrogant Age.

Jennifer Banks in Conversation with Anthony T. Kronman

BUFFALO, NY — October 27, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 17, 2025, titled “Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.”

In this study led by first author Jessica Louzame Ruano and corresponding author Maria A. Blasco from the Spanish National Cancer Centre (CNIO), researchers investigated the role of TRF1, a protein known for protecting telomeres, in regulating whole-body metabolism. The results suggest that TRF1 influences metabolic health through mechanisms unrelated to its known function in telomere maintenance.

Obesity and metabolic disorders are major health concerns, especially as people age. To explore TRF1’s role beyond telomere protection, the research team studied both normal mice and genetically modified mice that lacked TRF1. Mice without TRF1 remained leaner over time, resisted fat accumulation, and showed healthier blood sugar and insulin levels compared to normal mice. Importantly, these benefits occurred without any detectable shortening of telomeres.

The leaner body composition in TRF1-deficient mice was not due to reduced food intake or increased physical activity. Instead, the fat loss appeared to result from biological changes in how energy was processed and stored. Male mice without TRF1 gained less weight and had lower LDL cholesterol levels, even on a high-fat diet. Female mice showed milder effects, reflecting known sex-based differences in susceptibility to diet-induced obesity. This highlights the importance of including both sexes in metabolic research.

“Major metabolic pathways related with energy production and regulation of metabolism homeostasis were also found downregulated in Trf1-deficient mice.”

Gene expression analysis in the liver revealed shifts in several key pathways. Genes related to fat production, energy generation, and muscle growth were downregulated, while genes linked to inflammation and cholesterol synthesis were upregulated. The mice also showed signs of higher energy expenditure and a shift from using fat to protein as an energy source, possibly due to their reduced fat reserves. However, some older mice developed mild liver stress, including fibrosis and DNA damage, suggesting a possible long-term trade-off.

Overall, this study expands the understanding of how telomere-related proteins influence more than just cellular aging. By identifying a connection between TRF1 and metabolism, the research opens new possibilities for targeting TRF1 or its pathways to address obesity and related conditions. Still, further studies are needed to clarify how TRF1 affects fat development and whether similar effects occur in humans.

DOI - https://doi.org/10.18632/aging.206320

Corresponding author - Maria A. Blasco — mblasco@cnio.es

Abstract video - https://www.youtube.com/watch?v=7AG3TBgDZIw

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Keywords - aging, Trf1, metabolism, leaner, fat, telomeres

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TRF1 Protein Loss Reduces Body Fat and Improves Metabolic Health in Mice Without Shortening Telomeres

TRF1 Protein Loss Reduces Fat and Improves Metabolic Health in Mice Without Shortening Telomeres

Lauren Jackson is a religion columnist for the New York Times where she is the associate editor and writer for The Morning, the Times's flagship daily newsletter. Over the past year, she has been deeply involved in reporting on belief. Lauren developed 'Believing,' a project that explores how we experience religion and spirituality in contemporary times. Lauren's thought-provoking columns delve into the complexities of faith, spirituality, and society. In this episode of The Leader’s Way, Lauren discusses the powerful transformation that is possible when we turn our attention to the people around us, attending to hyper-local needs, longings, and joys within our own community.

Host: Brandon Nappi
Guest: Lauren Jackson

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69: Believing with Lauren Jackson

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

AGO2 in T-prolymphocytic Leukemia (T-PLL)

Oncotarget Podcast