Objective: To summarize the clinical characteristics, molecular genetic features, diagnosis and treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL) with myocyte enhancer factor 2D (MEF2D) gene rearrangement. Methods: In this case series study, clinical data of 9 children newly diagnosed B-ALL with MEF2D gene rearranged, admitted to the First Affiliated Hospital of Zhengzhou University from May 2020 to June 2025 were collected. The clinical characteristics, laboratory findings, treatment regimens, and outcomes of these patients were systematically analyzed. Results: A total of 9 chlidren were enrolled (3 boys and 6 girls), with the diagnostic age of 12.0 (11.0, 13.8) years. Five children initially presented with fever accompanied by arthralgia. Immunophenotyping revealed that 1 child was early precursor B-ALL and the remaining 8 children were common B-ALL. Uniformly high expression of CD38 and absence of cytoplasmic immunoglobulin M (cIgM) expression in all 9 children. Bone marrow smear examination demonstrated cytoplasmic vacuolization in 5 children. RNA sequencing detected 5 types of MEF2D gene fusion partners, including BCL9 gene in 4 children, FOXJ2 gene in 2 children, and 1 child each of DAZAP1 gene, SS18 gene, and ARNT gene. Heterozygous deletions of CDKN2A or CDKN2B gene were detected in 6 children, and 8 children exhibited concurrent gene variations. Induction therapy with the vincristine+daunorubicin+L-asparaginase+prednisone (VDLP) regimen was administered to all 9 children in accordance with＂the Clinical Practice Guideline for Childhood Acute Lymphoblastic Leukemia (2018)＂. At the end of induction remission therapy, minimal residual disease (MRD) assessed by flow cytometry were all negative (<0.01%) in all cases. One child was lost to follow-up during the maintenance phase. Three children experienced relapse and succumbed. The remaining 5 children were followed up until October 10, 2025, with 2 in disease-free survival and 3 still receiving regular treatment. Conclusions: B-ALL with MEF2D gene rearrangement predominantly affects older children, typically presenting with fever accompanied by arthralgia. This subtype exhibits high CD38 expression and absence of cIgM expression, with a frequent incidence of CDKN2A or CDKN2B gene deletions. Although the initial treatment response was good, the risk of recurrence was high and the efficacy of salvage treatment was limited. For this high-risk sub-type, the use of next-generation sequencing for MRD monitoring could be explored to more accurately assess the risk of relapse.

Objective: To investigate the clinical characteristics and prognostic factors of pediatric precursor lymphoid neoplasms with KMT2A gene rearrangement. Methods: In this retrospective cohort study, clinical data of 47 children with KMT2A gene rearrangement precursor lymphoid neoplasms diagnosed at the Children's Hospital Affiliated to Zhengzhou University from January 2018 to November 2024 were collected, so as to describe their clinical characteristics. According to whether hematopoietic stem cell transplantation (HSCT) was performed during first complete remission (CR1), children were divided into CR1 transplantation group and CR1 chemotherapy group, survival rates comparison and prognostic factor analysis were performed between two groups. For relapsed children in the CR1 chemotherapy group, they were further subdivided into a transplantation salvage group and a chemotherapy salvage group based on salvage therapy modality, and post-relapse survival rates were compared between the two subgroups. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were analyzed using the Cox proportional hazards regression model. Results: Among the 47 patients, there were 27 males and 20 females, with the age of 0.8 (0.4, 2.4) years. B-cell acute lymphoblastic leukemia accounted for 85% (40 cases). The initial white blood cell count was 89×10⁹ (27×10⁹, 302×10⁹)/L. Central nervous system leukemia was diagnosed in 10 children(22%, 46 children had central nervous system assessment). A total of 43 children were included in the efficacy evaluation, with a follow-up of 30.1 (13.8, 47.7) months. The 3-year overall survival and event-free survival (EFS) rates were (68.2±7.3) % and (51.7±8.0) %, respectively. The CR1 transplantation group (17 children) had significantly better 3-year overall survival and EFS rates than the CR1 chemotherapy group (26 children)(100.0% vs. (47.2±10.1) %, (84.7±10.3) % vs. (29.6±9.1) %, χ²=12.68 and 16.03, both P<0.001). The transplantation salvage group (4 children) had a higher 18-month overall survival rate than the chemotherapy salvage group (14 children) (100.0% vs. (8.9±8.4)%, χ²=10.07, P=0.002). Multivariate analysis showed that negativity of minimal residual disease detected by quantitative real-time PCR (qPCR-MRD) at week 12 of induction therapy (HR=0.29, 95%CI 0.10-0.83, P=0.022) and HSCT (HR=0.15, 95%CI 0.05-0.44, P<0.001) were both independent protective factors for EFS. Conclusion: Pediatric KMT2A gene rearrangement precursor lymphoid neoplasms are clinically highly aggressive and have a poor prognosis, but negative qPCR-MRD at week 12 of induction therapy and HSCT are independent protective factors for EFS.

Skin darkening can result from various factors, with prolonged sun exposure being a primary cause. α-Melanocyte-stimulating hormone (α-MSH) plays a crucial role in stimulating melanin production. However, our understanding of hyperpigmentation in individuals with cancer or rheumatoid arthritis (RA) remains limited. This study investigated the effect of autocrine motility factor (AMF) on hyperpigmentation.

We previously reported that Pyra-Metho-Carnil (PMC) suppresses macrophage differentiation in co-culture with mutant (mt) Kirsten rat sarcoma (KRAS) tumors. In this study, we used integrative proteomics and identified a KRAS-regulated membrane and exosomal protein, 5'-nucleotidase ecto (NT5E)/CD73, as a key candidate linking KRAS signaling to macrophage-associated tumor immune microenvironment (TIME) remodeling. We investigated whether PMC modulates CD73-associated pathways during macrophage differentiation.

Ulcerative colitis (UC) is associated with an increased risk of colitis-associated colorectal cancer (CAC), which develops through inflammation-driven carcinogenesis distinct from sporadic colorectal cancer (CRC). Reliable molecular markers to differentiate CAC from CRC remain limited. This study aimed to identify genes preferentially expressed in CAC and to evaluate their potential diagnostic relevance.

Kisspeptin signaling is recognized as a metastasis-suppressive pathway, but its role in oncogenic HRAS-driven tumor progression remains incompletely understood. This study investigated whether kisspeptin signaling suppresses HRASG12V-induced tumorigenic and metastatic phenotypes in NIH3T3 cells and examined the involvement of SP1-dependent transcription of N-cadherin.

Biliary tract cancer (BTC) is an aggressive malignancy associated with a poor prognosis, yet effective molecular therapeutic targets remain scarce. Chromosome 16 open reading frame 74 (C16orf74) has been implicated in tumor progression; however, its specific role in BTC remains unclear. This study aimed to investigate the prognostic significance of C16orf74 in extrahepatic cholangiocarcinoma (eCCA) and to evaluate its potential as a therapeutic target.

Chitinase 3-like-1 (CHI3L1/YKL-40) is a secreted glycoprotein that binds to chitin but lacks enzymatic activity. Recent studies have suggested that CHI3L1 nuclear localization is associated with the transition from inflammation to carcinogenesis. To investigate the mechanism underlying CHI3L1 nuclear translocation, we analyzed its putative nuclear localization signals (NLSs) using cNLS Mapper and identified 9 putative NLS sequences. The region with the highest scoring (amino acids 144-173) contains a leucine-rich KQLLL motif at its C-terminal end (residues 170-174). This study aimed to clarify the functional role of this motif.

Lung cancer remains the leading cause of cancer-related mortality worldwide, and cigarette smoking is its predominant factor. However, genetic biomarkers contributing to susceptibility, particularly within cell-cycle regulatory genes such as cyclin dependent kinase inhibitor 1B (CDKN1B), remain incompletely identified. The study aimed to investigate the contribution of CDKN1B rs34330 and rs2066827 polymorphisms to lung cancer risk, and to evaluate their interaction with smoking behavior in a Taiwanese cohort.

The prognostic relevance of erythropoietin receptor (EPOR) expression in clear cell renal cell carcinoma (ccRCC) remains incompletely defined. We evaluated whether EPOR expression is associated with overall survival in The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma cohort (TCGA-KIRC) and whether this association persists after joint adjustment for erythropoietin (EPO) expression.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by chemoresistance and metabolic reprogramming centered on glucose-6-phosphate dehydrogenase (G6PD)-dependent pentose phosphate pathway activity. Exogenously administered autocrine motility factor (AMF) suppresses G6PD at transcriptional and protein levels, elevating intracellular reactive oxygen species (ROS) to cytostatic thresholds. Glycyrrhetinic acid (GA), a bioactive triterpenoid from licorice root, amplifies oxidative stress through mitochondrial membrane disruption, while concurrently downregulating multidrug resistance-associated ABC transporters.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide and is characterized by an immunosuppressive tumor microenvironment (TME). While adaptive immunity contributes to tumor control, growing evidence underscores the role of innate lymphocytes, particularly natural killer (NK) cells, in early antitumor surveillance. However, tumor-infiltrating NK cells often exhibit defective maturation and impaired effector functions, whereas the signals regulating NK cell differentiation and activity in CRC remain poorly defined. Interleukin-27 (IL-27) has emerged as a regulator of antitumor immunity, yet its role in modulating NK cell responses in intestinal tumors is largely unexplored.

Although chromosome 14q deletion (14q-) is present in up to 40% of clear cell renal cell carcinoma (ccRCC) cases, its immunologic and molecular impact remains unclear. Because TRAF3 and NFΚBIA, key regulators of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, are located on 14q, we hypothesize that 14q- in ccRCC promotes increased inflammation and unique determinants of immune checkpoint blockade (ICB) response.

There is increasing recognition of the high prevalence of hereditary predisposition syndromes in patients diagnosed with paraganglioma/pheochromocytoma. It is widely acknowledged that germline pathogenic alterations of the succinate dehydrogenase complex genes (SDHA, SDHB, SDHC, SDHD, SDHAF2) contribute to the pathogenesis of most of these tumors. Herein, we have provided an update on the biology and diagnosis of succinate dehydrogenase-deficient paraganglioma/pheochromocytoma, including the molecular biology of the succinate dehydrogenase complex, mechanisms and consequences of inactivation of this complex, the prevalence of pathogenic alterations, and patterns of inheritance.

Mutational inactivation of the DICER1 gene causes aberrant micro-RNA maturation, which in turn may have consequences for the posttranscriptional regulation of gene expression, thereby contributing to tumor formation in various organs. Germline DICER1 mutations cause DICER1 syndrome, a pleiotropic condition with an increased risk of various neoplastic conditions in the pleura, ovaries, thyroid, pituitary, pineal gland, and mesenchymal tissues. Somatic DICER1 mutations are also frequently observed in a wide variety of solid tumors, thereby highlighting the importance of this gene in tumor development. In this review, the importance of DICER1 inactivation in endocrine tumors is discussed.

CDC73 alterations are associated with three main parathyroid lesions according to the World Health Organization (WHO) classification of tumors of the endocrine system. These include hyperparathyroidism-jaw tumor (HPT-JT) syndrome-associated adenomas, atypical parathyroid tumors (APTs), and parathyroid carcinomas (PCs). The loss of nuclear parafibromin expression, which serves as a surrogate marker for the underlying CDC73 alteration, encompasses these tumors under the term parafibromin-deficient parathyroid tumors. They have distinct morphologic features of more abundant eosinophilic cytoplasm with perinuclear clearing surrounding a large nucleus as well as prominent dilated branching "hemangiopericytoma-like" vasculature and a thick capsule as well as variably sized cystic spaces. These tumors include cases that show unequivocal histologic features fulfilling the criteria for PCs with growing data indicating a higher rate of recurrence or metastasis compared with parafibromin intact PCs. More importantly, the loss of parafibromin expression can be used in clinical practice to recognize APTs that fall short of a conclusive diagnosis of PCs, but clinically behave akin to them. Moreover, recognizing these tumors can lead to an underlying germline mutation and a diagnosis of HPT-JT, which impacts long-term treatment and surveillance for patients and close family.

This review aims to provide an overview of the molecular pathogenesis thyroid carcinomas, emphasizing genetic alterations that are therapeutically actionable. The main pathways in thyroid carcinogenesis are the MAPK and PI3K pathways. Point mutations and gene rearrangements affecting the pathway effectors and receptor tyrosine kinases are well-known drivers of thyroid cancer. Research over the past few decades has successfully introduced highly effective treatments for unresectable thyroid cancer, evolving from multi-kinase inhibitors to structurally selective agents, with constantly improving toxicity profiles and coverage of resistance mechanisms. The pros and cons of major laboratory techniques for therapeutic target identification are discussed.

Poorly differentiated thyroid carcinoma (PDTC) and differentiated high-grade thyroid carcinoma (DHGTC) are uncommon thyroid malignancies, recently (re)codified into distinct entities with overlapping clinical significance. Recognizing them may be challenging for the general practitioner and subspecialty pathologist alike. This article will describe the required features to diagnose PDTC and DHGTC, differential diagnostic considerations, molecular findings, and clinical implications. It is intended to be a general synopsis of the most critical elements of PDTC and DHGTC as well as a summary of points in approaching these challenging cases.

Risk stratification is essential in the preoperative evaluation and management of thyroid nodules, most of which are benign. Advances in DNA and RNA sequencing have shed light on the molecular drivers of thyroid cancer. Molecular testing of cytologically indeterminate nodules has helped refine risk stratification, triage patients for surgery, and determine the extent of surgery. Molecular platforms with high negative predictive values can help identify nodules that may be spared surgery and can be managed conservatively. Here we discuss the importance of integrating cytomorphologic, molecular, and histologic features to help avoid errors and improve patient management.

SUMOylation is implicated in the regulation of multiple malignancies. However, its potential roles in head and neck squamous cell carcinoma (HNSCC) remain insufficiently characterised. By integrating bulk RNA-seq, scRNA-seq and stRNA-seq datasets, we systematically interrogated the biological relevance of SUMOylation in HNSCC. Key markers from the signature were further validated using in vitro functional assays. A recognition model was established and validated using 692 HNSCC and 178 non-HNSCC samples. SROC analysis demonstrated robust performance across eight datasets (AUC = 0.92). Functional enrichment and scRNA-seq analyses indicated that SUMOylation may exert its effects in HNSCC primarily through cell-cycle regulation. Among the model features, SAE1 was markedly overexpressed in HNSCC (SMD = 1.07, 95% CI 0.56-1.59, p < 0.05). In vitro assays further confirmed that SAE1 enhanced proliferation, colony formation and migration in SAS and SCC-9 cells and validated its role in regulating cell cycle progression and apoptosis. We established a SUMOylation-related recognition model for HNSCC with consistently strong performance in multiple external validation cohorts. SAE1 emerges as a candidate molecular biomarker for HNSCC.