Chronic myeloid leukemia (CML) is a disease characterized by Philadelphia (Ph) translocations. These translocations can be classical or variant. The structural features and diagnostic implications of variant Philadelphia translocations remain incompletely defined, and they display considerable cytogenetic heterogeneity. In this retrospective study, variant Ph translocations identified by conventional cytogenetic analysis and fluorescence insitu hybridization (FISH) were systematically classified among 639 patients diagnosed with CML. A total of 35 patients with variant Ph translocations were included in the analysis. Molecular follow-up data, when available, were assessed using RT-qPCR analyses in a subset of patients. Chromosome analysis revealed 2 simple and 33 complex variant Ph translocations. FISH analysis, performed in 20 patients, identified deletions involving BCR, ABL1, or both in a limited number of cases. Additional chromosomal abnormalities and secondary translocations accompanied variant Ph translocations in four patients. The partner chromosomes involved in variant Ph translocations showed marked diversity, involving multiple chromosomal loci. Variant Philadelphia chromosome translocations in CML exhibit substantial cytogenetic diversity, reflecting the complexity of their underlying genomic architecture. The rarity and heterogeneity of these rearrangements complicate their classification and interpretation in routine diagnostic practice. Descriptive reporting of variant Ph translocations may contribute to a better understanding of their diagnostic complexity and support more accurate cytogenetic interpretation in CML.

BACKGROUND Tendon stem/progenitor cells (TSPCs) are a novel type of stem cell. TSPCs share common characteristics with stem cells, including their proliferation, pluripotency, and self-renewal abilities. Circular RNA plasmacytoma variant translocation 1 (circ_PVT1) has been reported to inhibit senescence in TSPCs. However, the mechanism by which circ_PVT1 regulates the proliferation and differentiation of TSPCs remains unclear. AIM To explore how circ_PVT1 regulates the proliferation and differentiation of TSPCs. METHODS Mouse TSPCs were isolated from the Achilles tendon of 12 male C57Bl/6 mice at postnatal day 30, and 5 ng/mL of transforming growth factor (TGF)-β1 was used to induce the tenogenic differentiation in TSPCs. Picro-Sirius red staining was used to detect the collagen expression of TSPCs. A Cell Counting Kit-8, Transwell assays, and flow cytometry were used to assess the proliferation, migration, and apoptosis of TSPCs. Biochemical kits were used to determine the levels of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, and ATP. Then, N6-methyladenosine (m6A) dot blot and methylated RNA immunoprecipitation polymerase chain reaction (RIP-PCR) were used to examine the m6A levels. Moreover, RNA pulldown and RIP-PCR were performed to analyze the interaction between WTAP and circ_PVT1. RESULTS TGF-β1 treatment induced tenogenic differentiation of TSPCs. Circ_PVT1 knockdown reversed the increase of tendon-specific protein, cell proliferation, and migration that was induced by TGF-β1 treatment. In addition, circ_PVT1 inhibition promoted oxidative stress and mitochondrial damage in the TGF-β1-induced TSPCs. The m6A modification level of circ_PVT1 was upregulated in the TGF-β1-induced TSPCs. Furthermore, RNA pulldown and RIP-PCR showed that circ_PVT1 interacted with WTAP in TSPCs, and the WTAP-mediated m6A modification of circ_PVT1 regulated the differentiation of TSPCs. CONCLUSION WTAP-mediated m6A modification of circ_PVT1 promotes the proliferation and tenogenic differentiation of TSPCs, thereby indicating a promising therapeutic strategy for tendon repair.

Chronic myeloid leukemia (CML) in chronic phase (CP) typically follows an indolent course. We report a highly aggressive pediatric case with a discordant presentation. A 10-year-old girl presented with rapidly progressive symptoms and hyperleukocytosis (WBC 448.7×109/L). Initial bone marrow examination was morphologically diagnostic for CML-CP (blasts 1%). Conventional cytogenetics revealed a complex three-way translocation, t(7;9;22)(q11.23;q34;q11.2). Despite immediate initiation of a second-generation tyrosine kinase inhibitor (TKI), the disease transformed to myeloid blast crisis (BC) within 1 month. This case demonstrates that complex variant translocations, in the absence of other risk factors by standard evaluation, may identify a subset of CML with exceptionally rapid kinetics and inherent TKI resistance. It underscores the high-risk nature of certain cytogenetic findings, even with classic CP morphology, and highlights the critical prognostic information contained in a basic karyotype. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

LncRNA PVT1 activates HIF-1α/RANKL signal to promote osteoclast differentiation and inflammatory response through post-transcriptional regulation.

Identification of genomic rearrangements by microarrays or short-read sequencing frequently lacks information about the exact architecture and breakpoints of variants due to technical limitations. Independent verification of complex structural variants (SVs) is often performed using custom targeted assays, making confirmation of clinically relevant findings time consuming and laborious. In this study we evaluate Oxford Nanopore long-read adaptive sampling for flexible and rapid confirmation and characterization of complex genomic rearrangements and structural variants. Adaptive sampling is an in silico target enrichment, where continued sequencing or ejection of a fragment is based on whether it matches a defined reference sequence. Using adaptive sampling, we targeted 10 regions with different structural variant types, including deletions, translocations, and complex rearrangements. Each sample was analyzed on a MinION or PromethION flow-cell, and sequencing resulted in between 14.1-18.3 Gb of data per sample, with mean autosomal on-target coverage of 28.4x and off-target read depth coverage of 5.3x. We were able to verify all 10 rearrangements, with breakpoint spanning reads for nine of the ten regions, and fully resolved the architecture ofnine regions. We also show that background reads can be used to detect structural variants in non-targeted regions of the genome. Our results show that adaptive sampling represents a flexible and rapid strategy for confirmation and characterization of clinically relevant genomic rearrangements in clinical samples. By providing sequence information, read depth, and methylation data, nanopore adaptive sampling has advantages over other assays for variant confirmation used in diagnostic laboratories today.

A small proportion of patients with acute promyelocytic leukemia (APL) harbor variant chromosomal translocations that lead to fusion of *RARA* to one of several alternative partner genes. The most frequently reported of variant is the t(11;17)(q23;q21), which generates the fusion of the zinc finger gene *ZBTB16* (formerly PLZF) to the *RARA* locus (*ZBTB16::RARA* fusion). This APL subtype is typically resistant to standard APL-directed therapies and most patients with this translocation relapse within one year with limited subsequent treatment options. Here, we report on a patient with *ZBTB16::RARA* APL who achieved durable molecular complete remission lasting more than two years after high-dose chemotherapy with busulfan and cyclophosphamide followed by autologous stem cell transplantation. This therapeutic approach has not previously been described for this rare APL variant and may represent a promising consolidation strategy in selected patients. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Stefan Balabanov, Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland Prof. Dr Alicia Rovó, Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Received on January 19, 2026; accepted after peer review on February 19, 2026; published online on February 23, 2026.

To investigate the mechanisms underlying the protective effects of piperine on retinal pigment epithelium (RPE) cells under high-glucose and hypoxic conditions. A model of diabetes was established by treating D407 cells with high glucose (25 mM) and hypoxia (5% O2 for 24 h). The mRNA and protein expression levels of the long noncoding RNA (lncRNA), plasmacytoma variant translocation 1 (PVT1), miR-128, pigment epithelium-derived factor (PEDF), and vascular endothelial growth factor C (VEGFC) were assessed by RT-qPCR, western blotting, and immunofluorescence staining. Wound-healing assays were performed to evaluate cell migration. The role of PVT1 was explored using siRNA-mediated knockdown, and the interactions among lncRNA PVT1, miR-128, and VEGFC were predicted and validated by dual-luciferase reporter assays. Under high-glucose and hypoxic conditions, lncRNA PVT1 and VEGFC mRNA transcription were upregulated, whereas miR-128 and PEDF mRNA expression were downregulated. VEGFC protein levels were increased, PEDF protein levels were decreased, and cell migration was impaired. Treatment with piperine or knockdown of lncRNA PVT1 via siRNA partially reversed these effects. Dual-luciferase reporter assays further confirmed the interactions among PVT1, miR-128, and VEGFC. Piperine may protect RPE cells by modulating the lncRNA PVT1/miR-128 signaling pathway and promoting PEDF expression.

Background/aimChronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome (Ph), which occurs as a result of t(9;22). In 5%–10% of CML cases, variant t(9;22)s are observed. Additionally, while t(9;22) is formed, deletions can be observed in chromosomes 9 and 22. These deletions are observed more frequently in variant t(9;22). There is conflicting information in the literature about the prognostic effects of variant t(9;22) and deletions of 9q and 22q. There is also limited information about the frequency and breakpoints of other chromosomes involved in the variant t(9;22). Signal patterns other than the classical signal pattern of FISH analysis indicate deletions and variant translocations. In this study, we aimed to investigate the clinical significance of nonclassical FISH signal patterns and to determine the frequency of variant translocations.Materials and methodsBone marrow samples from 231 newly diagnosed CML patients were analyzed by conventional cytogenetics and FISH.ResultsAs a result of FISH analysis, nonclassical FISH signal patterns were detected in 49/231 cases, and variant t(9;22) was detected in seven cases by conventional cytogenetics. It was determined that chromosomes 1, 3, 5, 7, 8, and 21 were involved in variant t(9;22). When cases with classical and nonclassical signal patterns were compared in terms of 6th- and 12th-month treatment responses, survival times, and treatment changes, it was found that cases with classical signal patterns had significantly higher treatment responses at the 6th month (p < 0.001).ConclusionBecause variant translocations are extremely rare and involve many different chromosomal breaks, a large number of cases are needed to clearly understand their prognostic implications. Due to the limitations of conventional cytogenetic analyses, it should be considered in patient follow-up that nonclassical FISH signal patterns indicating deletions and/or variant translocations may cause a delay in obtaining a complete cytogenetic response at the 6th month.

PVT1 is a non-coding RNA (ncRNA) playing an important role in various biological processes, including cell survival, differentiation, proliferation, and chromatin regulation. Overexpression of PVT1 improve a proliferation rate even for 30% and reduces the level of apoptosis. It can act as a scaffold, decoy, guide, enhancer RNA, and it affects the entire gene life cycle through chromatin remodeling, epigenetic regulation, transcription, post-transcriptional control, and protein metabolism. PVT1 is a highly complex and multifunctional factor that plays a critical role in cancer development and progression through various mechanisms. Different PVT1 fusion transcripts have been identified in solid tumors and hematological malignancies. High expression of PVT1 is linked to advanced clinical stage, lymph node metastasis, and unfavorable overall survival in various types of human cancers. The manuscript represents extensive analysis and summary of the functions and mechanisms of PVT1 in the context of miRNAs and highlights possible ways to target PVT1 and the it signaling pathways. It is important to understand the intricate relationships between PVT1 and different types of human cancers to achieve a better understanding of the disease and treatment options. The current findings identify an upregulated PVT1 as a crucial promoter of the risk of carcinogenesis and tumor metastasis, also dramatically reducing patient survival, underscoring the potential of PVT1 expression as a prognostic marker in cancer.

PVT1 (Plasmacytoma Variant Translocation 1), a long non-coding RNA (lncRNA), is a critical player in diverse biological processes, particularly cancer biology. This review comprehensively examines PVT1’s multifaceted roles and molecular mechanisms. We delve into its predominant oncogenic functions while highlighting notable exceptions, offering new perspectives on its biological diversity. A key focus is the subcellular localizations of PVT1 across various cancers – an aspect underexplored in previous reviews despite its significant impact on function and regulatory mechanisms. Detailed mechanistic insights include PVT1’s linear and circular isoforms acting as miRNA sponges, its encoding of miRNAs, the influence of 8q24 rearrangements, and its regulation of protein stability/activity, and transcription. Furthermore, we examine PVT1’s functional elements, illuminating unexplored structural and regulatory features. The clinical implications of PVT1 as a biomarker and therapeutic target in oncology are also discussed. By synthesizing existing knowledge and introducing previously less-explored facets, this review aims to provide a comprehensive and up-to-date resource on PVT1’s role in health and disease.

Abstract Prostate cancer remains a major global health concern and disproportionately affects Black men/men of African ancestry (MoAA). Compared to men of European ancestry (MoEA), MoAA experience both a higher incidence of prostate cancer and significantly elevated mortality rates. According to recent American Cancer Society reports, MoAA have a 67% higher incidence of prostate cancer and are more than twice as likely to die from the disease. While socioeconomic and healthcare access factors contribute to these disparities, growing evidence suggests that underlying molecular mechanisms also play a critical role. One emerging molecular factor is the long non-coding RNA Plasmacytoma Variant Translocation 1 (PVT1), which is consistently overexpressed in prostate tumors from MoAA. Prior studies have implicated PVT1 exon 9 in promoting tumor development and progression. Experimental overexpression of exon 9 in prostate cancer models increases tumor aggressiveness and enhances malignant cellular behavior, supporting a functional role in disease severity. In addition, PVT1 exon 9 induces malignant transformation of prostate epithelial cells. However, recent findings indicate that PVT1 is not expressed as a single transcript, but rather as a diverse set of alternatively spliced isoforms, raising the possibility that specific variants may contribute to the observed racial disparities. We hypothesize that a subset of these alternatively spliced PVT1 transcripts is differentially expressed in MoAA and contributes to the increased prostate cancer incidence and mortality observed in this population. To investigate this, we analyzed PVT1 splicing profiles using prostate cancer datasets from two independent studies, including TCGA. We identified ENST00000666076, an alternatively spliced PVT1 transcript located on Chromosome 8: 27,975,972–27,995,613, as being significantly overexpressed in MoAA compared to MoEA. This transcript includes five exons: ENSE00004271579, ENSE00004271636, ENSE00002081483, ENSE00002020395, and ENSE00004271500. In conclusion, our analysis supports emerging reports that distinct PVT1 splice variants may be involved in prostate cancer carcinogenesis. Citation Format: Seidu Adams, Dominique Weatherall, Rachel E. Bonacci, Chinedum C. Udekwu, Olorunseun O. Ogunwobi. Long non-coding RNA Plasmacytoma Variant Translocation 1 Alternative Splicing in Prostate Carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A006.

To analyze on the role of long-chain non coding ribonucleic acid (LncRNA) plasmacytoma variant translocation 1 (PVT1) in the differentiation of dental pulp mesenchymal stem cells (DPMSCs) into dentin by targeting microribonucleic acid 18b-5p(miR-18b-5p). Human DPMSCs were isolated and cultured, then identified by staining with oil red O, Alizarin red, and Alisin blue, and detected cell surface marker molecules by flow cytometry. Inoculate cells onto a 24 well plate, 2×104/cm2 density, grouping, including PVT1 upregulation+miR-18b-5p downregulation group (transfected with pcDNA-PVT1 and antomiR-18b-5p), PVT1 downregulation+miR-18b-5p upregulation group (transfected with si-PVT1 and agomiR-18b-5p), empty 1 group (transfected with NC pcDNA), empty 2 group (transfected with ago-NC), PVT1 upregulation + empty 2 group (transfected with pcDNA-PVT1 and empty 2). empty1+miR-18b-5p downregulation group (transfected with empty1 and antomiR-18b-5p) and a blank group. After 7 days, Alizarin red staining was used to observe the calcium mineralization of cells, and alkaline phosphatase (ALP) activity was detected using a reagent kit. Real time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the expressions of LncRNA PVT1, miR-18b-5p, dentin salivary phosphoprotein(DSPP), osteocalcin(OCN), and Runt related transcription factor 2 (RUNX2) genes in each group. Western blot(WB) was used to detect the expressions of DSPP, OCN, and RUNX2 proteins in each group. Dual luciferase reporter gene detection experiment was used to explore the targeting relationship between LncRNA PVT1 and miR-18b-5p. This study successfully isolated human DPMSCs and identified them by staining with oil red O, Alizarin red, Alishin blue and flow cytometry. The PVT1 upregulation+miR-18b-5p downregulation group had the strongest dentin differentiation activities (P＜0.05), while that of PVT1 downregulation+miR-18b-5p upregulation group was the weakest(P＜0.05). The LncRNA PVT1, DSPP, OCN and RUNX2 expressions were highest in the PVT1 upregulation+miR-18b-5p downregulation group(P＜0.05), while miR-18b-5p expression was lowest (P＜0.05). The PVT1 downregulation+miR-18b-5p upregulation group showed the opposite trend(P＜0.05). There were binding sites between LncRNA PVT1 and miR-18b-5p, and LncRNA PVT1 could negatively feedback and target miR-18b-5p. Upregulation of LncRNA PVT1 can target the inhibition of miR-18b-5p and promote the differentiation of human DPMSCs into dentin, which may be related to the upregulation of DSPP, OCN and RUNX2 expressions.

Effect of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) on epithelial barrier in chronic rhinosinusitis with nasal polyps.

Prostate-specific antigen (PSA), a common screening tool for prostate cancer (PCa), has a high false-positive rate and is largely suboptimal. PSA is also weakly validated in men of African ancestry (moAA), who disproportionately bear the disease burden, necessitating investigation into its widespread use. Previously, we found that plasmacytoma variant translocation 1 (PVT1) exons 4A, 4B, and 9 are overexpressed in PCa tissues. Here, we report on the first serum-based evaluation of these exons to determine their utility in improving detection and risk stratification of PCa. Total RNA was extracted from serum samples obtained retrospectively from 144 multiracial men with elevated PSA who underwent prostate biopsy. Likelihood ratio test was used to evaluate the potential benefit of utilizing these alone or in combination with PSA. Regression analysis was used to evaluate the association of individual biomarkers with the odds of PCa and for evaluating endpoint predictions. Model generalizability was assessed using cross-validation and area under the receiver operating characteristic curve (ROC-AUC). All statistical tests were performed at a 5% level of significance using the Sklearn library in Python. Our results indicate that combining PSA with PVT1 exon 4A or 9 improves PCa risk stratification in the general population, increasing AUC from 0.72 to 0.75 as well as PCa detection, increasing specificity from 0.41 to 0.59. Within moAA, combining PSA with PVT1 exon 4A improves PCa detection substantially, increasing AUC from 0.44 to 0.67. Remarkably, PVT1 exon 4A alone achieves an AUC of 0.79. Our study provides preliminary exploratory evidence to support PVT1 exon 4A and PVT1 exon 9 as promising PCa risk biomarkers that can reduce disparity in PCa detection and management. Further validation in larger patient cohorts will be necessary to establish the clinical utility of these novel biomarkers.

Cholangiocarcinoma, a malignant tumor originating from the bile duct epithelium, poses significant therapeutic challenges and is often associated with poor prognosis. This study aims to elucidate the relationship between plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA implicated in cancer progression, and suppressor of cytokine signaling 2 (SOCS2), recognized for its tumor-suppressive properties. Utilizing the GEPIA2 database, we investigated the expression levels of PVT1 and SOCS2 in cholangiocarcinoma specimens and cell lines through quantitative real-time PCR (qRT-PCR) and Western blotting. Our results demonstrated that PVT1 expression was markedly upregulated in cholangiocarcinoma tissues and cells, while SOCS2 was significantly downregulated. Functional assays revealed that silencing PVT1 inhibited cholangiocarcinoma cell proliferation, migration, and invasion, suggesting its oncogenic role. Conversely, SOCS2 overexpression diminished these malignancies, highlighting its tumor-suppressive function. Notably, the knockdown of PVT1 correlated with an increase in SOCS2 expression, underscoring the regulatory interplay between these two molecules. Ultimately, our findings indicate that lncRNA PVT1 facilitates cholangiocarcinoma progression by repressing SOCS2 expression, positioning SOCS2 as a potential therapeutic target, and warranting further exploration in therapeutic strategies against cholangiocarcinoma.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-34019-x.

Acute promyelocytic leukemias (APL) with variant translocations involving the RARA gene at 17q21.2 with non-PML partners constitute a rare and diverse subset of APLs, accounting for approximately 5% of total cases. Variant APLs present considerable diagnostic challenges, as standard testing methodologies targeting the PML::RARA fusion protein are unrevealing, leading to a lack of diagnosis. We present the case of a 54-year-old patient with APL harboring a TBL1XR1::RARA fusion, an exceptionally rare APL variant that showed distinctive morphologic, phenotypic, and clinical attributes. Unlike conventional APL, the neoplastic promyelocytes lacked pathognomonic Auer rods and bilobed nuclei and were accompanied by marked granulocytic dysplasia and significant monocytosis. Phenotypically, the blasts were negative for CD117 and showed an associated expanded monocyte population with aberrant CD56 and CD23 expression, features highly uncharacteristic of classic APL. Cytogenetic analysis and targeted PCR yielded negative results for PML::RARA fusion; however, the break-apart probe analysis tested positive for a RARA rearrangement, ultimately facilitating an accurate diagnosis. The patient did not respond to all-trans retinoic acid (ATRA) and succumbed to the disease 24days after the initial presentation. This case brings to light the diagnostic challenges posed by variant APLs that may demonstrate divergent morphologic and phenotypic features and carry translocations that render the routine PML::RARA fusion-based methodologies futile. Accurate diagnosis requires a high index of suspicion and a comprehensive multifaceted diagnostic strategy that encompasses morphologic assessment, immunophenotypic analysis, RARA break-apart probe analysis supplementing traditional fusion probe techniques, conventional karyotyping, and advanced molecular fusion testing.

The T‐cell Leukemia Homeobox 1 (TLX1) oncogene is frequently deregulated in T‐cell acute lymphoblastic leukemia (T‐ALL) and T‐cell lymphoblastic lymphoma (T‐LBL). In most instances, TLX1 overexpression results from its juxtaposition with a T‐cell receptor (TCR) locus caused by interchromosomal translocations. However, in the subset of non‐TCR‐translocated TLX1‐positive (non‐TCR TLX1+) T‐ALL cases, the underlying mechanisms driving TLX1 overexpression and their clinico‐biological implications remain unclear. By integrating high‐resolution data from next‐generation sequencing, fluorescence in situ hybridization, karyotyping, optical genome mapping, and long‐read whole‐genome sequencing across a cohort of 1122 adult and pediatric T‐ALL/T‐LBL cases, we identified TLX1 overexpression in 11% of T‐ALL/T‐LBL cases, with an unexpected 14% incidence of non‐TCR TLX1+ cases among TLX1+ cases. Non‐TCR TLX1 + T‐ALL cases show distinct clinico‐biological features, including a lower frequency of cortical phenotype compared to the TCR‐translocated TLX1+ (TCR TLX1+) subgroup, regardless of TLX1 expression levels. In non‐TCR TLX1⁺ cases, TLX1 deregulation results mostly (83%) from the hijacking of the ANKRD1 and PCGF5 enhancer at 10q23.31 through various chromosomal aberrations. Genomic analyses revealed that these aberrations juxtapose the ANKRD1 and PCGF5 enhancer with TLX1, driving its overexpression. Importantly, survival analysis revealed that non‐TCR TLX1+ patients had significantly poorer outcomes compared to their TCR TLX1⁺ counterparts (3y‐OS: 55% vs. 90%, P < 0.001 and 3y‐DFS: 45% vs. 75%, P = 0.02). These findings, consistent with our previous observations in TAL1‐driven T‐ALL, confirm that the clinico‐biological impact of an oncogene is influenced by the specific mechanism underlying its deregulation.

BackgroundThis study aimed to investigate the potential causal relationship between plasma lipidome and non-small cell lung cancer (NSCLC) using a two-sample Mendelian randomization (MR) approach based on large-scale genome-wide association study (GWAS) data.MethodsA two-sample bidirectional MR analysis was conducted using summary-level data from the GeneRISK and FinnGen GWAS. Genetic instruments were selected for 179 plasma lipid traits. Causal effects were estimated using inverse variance weighting (IVW), MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Spatial transcriptomic profiling and machine learning–based gene prioritization were further employed to explore potential mechanistic links.ResultsMR identified 30 lipid species significantly associated with NSCLC risk, of which 17 demonstrated consistent causal effects across multiple sensitivity analyses. A subset of phosphatidylcholine and phosphatidylethanolamine species exhibited inverse associations, indicating potential protective effects, while specific sterol esters, sphingomyelins, and triacylglycerols were positively associated with disease susceptibility. Plasmacytoma Variant Translocation 1 (PVT1) was first prioritized as a key lipid-associated gene by three machine learning algorithms and was subsequently validated by spatial transcriptomics, showing elevated expression in tumor-dense regions.ConclusionThis study reveals a causal link between distinct plasma lipid species and NSCLC risk, emphasizing the role of lipid structural diversity. PVT1 may act as a critical mediator connecting lipid dysregulation to lung tumorigenesis, offering novel biomarker and therapeutic target potential.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12672-025-03823-2.

Background: Accurate detection of recurrent chromosomal translocations is essential for risk stratification and therapeutic decision-making in acute myeloid leukemia (AML). Although innovative techniques are becoming increasingly accessible, further improvements in conventional assays remain valuable. Although numerous translocations have been identified, the most frequent ones with prognostic value are limited. Objectives: In the present study, we developed a screening assay applicable in multiplex formats, using the same reagents, instruments, and conditions for screening the three most frequent translocations: RUNX1-RUNX1T1, PML-RARA, and CBFB-MYH11. Methods: A SYBR-Green real-time multiplex PCR was developed to simultaneously screen four frequent translocation variants in AML, including RUNX1-RUNX1T1, PML-RARα, bcr1, PML-RARα, bcr3, and CBFB-MYH11 type A. The ABL gene served as a reference and was amplified in separate reactions. Fifty newly diagnosed AML patients were chosen based on the availability of sufficient RNA quantity and quality, along with confirmed cytogenetic or molecular diagnosis according to the World Health Organization (WHO) 2022 classification criteria. The assay was validated by comparing the results with those obtained from singleplex real-time PCR in AML patients. Results: All four targets could successfully amplify in the master mix, containing seven primers, with no interference in their respective melting curves. Specificity was 100% for all targets. The intra-assay and inter-assay coefficient of variation (CV) for cycle threshold (Ct) values ranged from 0.68% to 1.12% and 0.22% to 1.02%, respectively. The validation assessments reported excellent consistency between singleplex and multiplex real-time PCR. However, the assay does not detect all CBFB-MYH11 variants or the bcr2 isoform of PML-RARα because of overlapping melting temperature (Tm). Despite these limitations, this multiplex assay could be considered a valuable first-line screening tool. Conclusions: This method provides a simple, accurate, cost-effective, and informative tool for screening these translocations in AML. Since the primers were previously validated in the singleplex method, this assay is simple and does not require particular materials or instruments. This novel assay may improve patient stratification, support more precise therapeutic planning, and represent an important advancement in molecular diagnostics.

BackgroundApproximately 50% of colorectal cancer (CRC) patients exhibit high levels of Fusobacterium nucleatum (Fn), which is associated with chemotherapy resistance. As Fn itself cannot be directly targeted for therapy in vivo, elucidating the mechanism underlying Fn-induced chemotherapy resistance is crucial, though it remains unclear.MethodsqPCR was used to analyze the correlation between Fn abundance and clinical parameters in 80 human colon cancer samples. The effect of Fn on the sensitivity of colon cancer cells to oxaliplatin was evaluated by clone formation, EdU proliferation and apoptosis assays. RNA sequencing was performed on Fn-infected colon cancer cells to identify differentially expressed genes. Mechanistic studies explored the interaction between PVT1 and ATAD3A, and the role of TLR4/NF-κB pathway in regulating PVT1 expression.ResultsqPCR experiments showed that Fn abundance was associated with later clinical stage and shorter RFS. Clone formation, EdU proliferation assay and apoptosis assay showed that Fn could change the sensitivity of colon cancer cells to oxaliplatin. Further RNA sequencing showed that Fn infection could upregulate the expression of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) in colon cancer cells. The abundance of Fn in colon cancer tissues was positively correlated with the level of PVT1, and the mechanism was that PVT1 binds to AAA domain protein 3 (ATAD3A) and prevents its ubiquitination. Fn upregulates ATAD3A expression through PVT1 and inhibits ER stress-mediated cell death. In addition, in colon cancer cells co-cultured with Fn, PVT1 expression is regulated by the TLR4/NF-κB pathway.ConclusionsThis study delineates a pathway where Fn infection promotes oxaliplatin resistancein colon cancer cells by upregulating PVT1 via the TLR4/NF-κB pathway. PVT1 subsequently stabilizes ATAD3A, suppressing cell death. PVT1 is a potential target to overcome the high abundance of Fusobacterium nucleatum leading to oxaliplatin resistance in colon cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-07226-3.