Search Results (1,239)

Bovine leukemia virus (BLV) is an oncogenic deltaretrovirus that infects B cells, and its possible presence in humans has garnered increasing attention. This study included 58 participants: 11 with B-cell precursor acute lymphoblastic leukemia (B-ALL, cases) and 47 healthy individuals (controls). Researchers assessed anti-gp51 antibodies and BLV proviral DNA in bone marrow and blood samples. Seropositivity was observed only in the B-ALL group (18.2%; 2/11), while all controls were seronegative. Quantitative PCR targeting the pol gene detected proviral DNA in 74.1% of samples, with similar detection rates between cases and controls. Although proviral load was higher in controls, this difference did not reach statistical significance. Conventional and nested PCR for other viral genes revealed a differential pattern: amplification of the tax gene was significantly associated with B-ALL, whereas gag and env were not. Bayesian Chow–Liu network analyses identified dependencies among viral genes and suggested that contextual factors, such as fieldwork, may influence the association between molecular positivity and B-ALL. Sequence analyses showed that the detected BLV strains clustered with previously reported bovine and human sequences from Colombia, all within genotype 1. These findings support human exposure to BLV and raise important questions about its persistence and potential connections to hematological diseases in humans. Full article

Acute Lymphoblastic Leukemia (ALL) is a heterogeneous hematological malignancy in which disease progression and response to therapy are influenced by a complex network of molecular alterations, interactions with the bone marrow microenvironment, and epigenetic modulation mechanisms. Crosstalk between oncogenic, inflammatory, and immunoregulatory signaling pathways, together with epigenetic modifications, contributes to the maintenance of leukemic survival and the development of therapeutic resistance. This review analyzes the role of cytokines and chemokines such as IL-6, TNF-α, and CXCL12, which act as biological biomarkers and key mediators of leukemia niche remodeling, and the main signaling pathways involved in ALL, such as Wnt/β-catenin, JAK/STAT, PI3K/AKT/mTOR, Notch, and BCR, highlighting their functional interconnection with the tumor microenvironment. The role of epigenetics in modulating the dialogue between leukemia cells and stromal components is also discussed. Epigenetic programs govern leukemia’s dependence on stromal support, inflammatory and niche-derived signals, as well as the microenvironment signaling pathways. Overall, targeting leukemia-niche interactions is a crucial strategy for improving outcomes in ALL and to identify potential molecular vulnerabilities, also for developing new therapeutic approaches for the treatment of the disease. Full article

Central nervous system (CNS) evaluation for leukemic involvement is essential both at initial diagnosis and throughout relapse surveillance in childhood acute lymphoblastic leukemia (ALL). Accurate CNS risk classification is a cornerstone of individualized chemotherapy and has significantly advanced treatment strategies. However, detecting leukemic cells in the cerebrospinal fluid (CSF) is challenging, particularly when only a small number of cells are present. While cytomorphology remains a standard diagnostic method, it is limited by low sensitivity and interobserver variability, especially in low-cellularity or equivocal samples. Flow cytometry offers superior sensitivity and specificity and is increasingly recommended to confirm or clarify ambiguous findings. Current guidelines support the use of both cytomorphologic review and flow cytometry to maximize diagnostic accuracy. Evidence consistently demonstrates that any detectable CSF blasts—even in the setting of low WBC counts—are associated with increased risk of CNS relapse and poorer outcomes, underscoring the importance of risk-adapted CNS-directed therapy. Although the prognostic significance of isolated flow-only positivity remains under study, emerging data suggest that timely therapeutic intensification may mitigate adverse outcomes. Additional modalities, including advanced flow cytometry and molecular assays, may further refine CSF assessment in the future. This review summarizes current diagnostic approaches and highlights the need for standardized protocols for CSF evaluation in pediatric ALL. Full article

Background/Objectives: Children with acute lymphoblastic leukemia (ALL) often experience treatment-related side effects. Physical therapy (PT) surveillance programs are helpful in identifying impairments; however, they do not typically incorporate assessments for peripheral neuropathy, motor proficiency, and foot drop. Our aim is to explore the feasibility of conducting additional functional tests to an existing surveillance program to improve the identification of impairments and characterize the prevalence of treatment-related deficits in children with ALL. Methods: A prospective, longitudinal descriptive study, embedded into a quality improvement initiative, was conducted. The surveillance program included standard assessments for ankle range of motion, activity level, balance, functional capacity, pain, gait, and kneeling to standing. Additional tests included motor and sensory function, foot posture, motor performance, quality of life, feasibility (recruitment and completion rates), service provision, and self-reported symptoms. Data were collected over 3 months. Results: Twenty children completed the study and 19 completed all assessments. Nineteen children presented deficits in at least two physical function tests. The most prevalent deficit identified from standard PT tests included decreased ankle range of motion (n = 19; 95%), and the most common deficit seen in the additional tests was impaired motor and sensory function (n = 14/19; 74%). Pain was the most common self-reported symptom in the checklist and the second worst subscale score in the pain dimension of the quality of life questionnaire (p < 0.001). Conclusions: Several treatment-related deficits were identified in children with ALL. Further research is warranted to explore the use of a standardized symptom checklist for the timely identification of functional limitations and impairments. Full article

Background/Objectives: Molecular subtyping of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has improved patient outcomes through stratification and selection of targeted therapies. Despite extensive genomic and transcriptomic profiling of this cancer, few studies to date have characterized the proteomic landscape, although proteins are the direct targets of many therapeutic agents. Methods: In this study, we demonstrate the utility of multi-omic integration of global transcriptomic, proteomic, and phosphoproteomic profiles of samples from patients diagnosed with either of two B-ALL subtypes—Ph-like (BCR::ABL1-like) and ETV6::RUNX1. Through individual and multi-omic analysis, we recapitulate known transcriptomic findings and identify novel subtype-specific proteomic and phosphoproteomic biomarkers. Conclusions: Our findings suggest a previously undescribed role for calcium-dependent signaling processes in Ph-like B-ALL, which has the potential to serve as a novel avenue for targeted treatments. By integrating multiple -omics modalities, we identify not only features of interest but also begin to unravel the regulatory interactions driving subtype-specific mechanisms of leukemogenesis. This integrated analytic approach paves the way for enhanced precision medicine for precise subtyping and treatment selection for pediatric leukemia patients. Full article

Hematopoietic stem cell transplant (HSCT) is a curative therapy for acute lymphoblastic leukemia (ALL), but its success is limited by chronic graft-versus-host disease (cGvHD) and disease relapse. A central challenge is uncoupling the graft-versus-leukemia (GvL) effect from cGvHD. Early changes in the bone marrow microenvironment following HSCT may offer a predictive window into these divergent outcomes. We conducted a retrospective, single-center, exploratory study on 14 pediatric ALL HSCT patients. Applying single-cell antibody-sequencing (AbSeq) on archived bone marrow aspirates collected 60–100 days post-HSCT, we evaluated immune patterns associated with the development of cGvHD or ALL relapse after day 114. cGvHD after day 114 was associated with upregulation of the endoplasmic reticulum (ER) stress transcription factor XBP1 in transitional B cell and IgM memory B cell populations, a mincle^highPD1⁻ neutrophil population, and exhausted LAG3⁺ effector memory T cells (T_EM). ALL relapse after day 114 was associated with higher CD22, CD24, and ARG1 expression in M(IL-4)-like macrophages and exhausted TIGIT⁺ T_EM. Results from this exploratory study suggest that marrow immune signatures of B cell ER stress preceding later development of cGvHD and macrophage-mediated immune evasion preceding relapse may potentially be early biomarkers for separating GvL from cGvHD in ALL HSCT. Validation with larger cohorts is warranted. Full article

Background/Objectives: B-cell precursor acute lymphoblastic leukemia (B-ALL), the most common pediatric acute leukemia (AL), is frequently characterized by aberrant antigen expression, which aids diagnosis and prognosis. The myeloid antigen CD66c is notably frequent in B-ALL and has been proposed as a marker of disease aggressiveness and treatment response. Evaluating CD66c in Mexican pediatric patients may provide insights into disease biology. Methods: A cohort of 128 pediatric patients was referred to the Laboratory of Oncoimmunology and Cytomics of Childhood Cancer (OCL) at Instituto Mexicano del Seguro Social (IMSS) for immunophenotyping tests between March 2022 and November 2023. Additionally, control bone marrow (BM) samples were assessed. Aberrant antigen expression in hematopoietic populations and BM microenvironment stroma phenotyping were performed. Results: In total, 84.38% of B-ALL patients exhibited aberrant expression of ≥1 myeloid antigen. Among CD66c-positive patients, 13.79% had detectable measurable residual disease (MRD) during follow-up and 20.69% died. Mesenchymal stromal cells (MSCs) from patients with positive or low CD66c expression displayed inflammatory profiles. ProB leukemias with low CD66c expression were more likely to exhibit detectable MRD, increased mortality, and reduced survival. Conclusions: Low CD66c expression induces molecular stealth that could favor immune evasion and niche persistence, thereby increasing the risk of relapse and therapeutic failure. Full article

Background: The potent synthetic glucocorticoid (GC), dexamethasone (DEX), is a highly effective component of conventional chemotherapy for acute lymphoblastic leukemia (ALL). However, cases of GC resistance require elucidation of the underlying mechanisms and the development of new strategies to overcome them. GC-induced autophagy can play a dual role in GC resistance: it often acts as a salvage mechanism in resistant cells, while in sensitive cells, it is a mechanism leading to cell death. Methods: In the present study, cell death and autophagy, as well as their dependence on glucocorticoid receptors (GRs), were simultaneously monitored in DEX-treated ALL cell lines, both sensitive and resistant to GCs. Results: In GC-resistant cell lines, no changes in autophagy levels were observed after DEX treatment, whereas in GC-sensitive cell lines, autophagy elevation was associated with cell death. Blockade of GC receptors completely abolished DEX cytotoxicity in CCRF–CEM cells but not in RS4;11 cells, suggesting the participation of distinct, cell line-specific mechanisms. Furthermore, we investigated how pharmacological modulation of autophagy, both induction and inhibition, affects GC sensitivity. Autophagy induction with tamoxifen (TAM) successfully sensitized most cell lines to DEX. In CCRF–CEM cells, the sensitization effect was shown to correlate with increased apoptosis. In other cell lines, no increase in cell death was observed, suggesting decreased cell proliferation. Conclusions: These results suggest that each ALL cell line may have an optimal basal level of autophagy, and targeted dysregulation of this level may be an effective strategy for enhancing GC sensitivity. Full article

Background/Objectives: This pilot study aimed to evaluate the metabolic profiles in plasma and cerebrospinal fluid (CSF) of 14 patients with acute lymphoblastic leukemia (ALL) and plasma of a control group, using proton magnetic resonance spectroscopy (¹H NMR). Methods: Multivariate analysis, including orthogonal partial least-squares discriminant analysis (OPLS-DA), was used to analyze the metabolome composition. Results: Significant differences in plasma metabolic profiles were found between the ALL and control groups. We detected elevated levels of formate, citrate, and glycerophosphocholine (GPC), along with decreased concentrations of glutamine and myo-inositol. The OPLS-DA model showed stability, with R²Y = 69.7% and Q² = 45.15%. Additionally, we observed differences in chemical shifts for leucine, myo-inositol, alanine, phenylalanine, and valine between CSF and plasma in patients with ALL. Conclusions: Our findings suggest that metabolomic analysis with ¹H NMR is a promising tool for identifying potential molecular biomarkers and for deepening our understanding of metabolic reprogramming in pediatric ALL. The observed metabolic differences highlight the potential involvement of the central nervous system in the disease’s pathophysiology. Full article

Background: Cardiorespiratory fitness is frequently impaired in survivors of pediatric acute lymphoblastic leukemia (ALL), limiting their functional performance. While aerobic exercise is recommended, evidence is needed to guide the prescription of specific training protocols in this population. Objective: This study sought to compare the efficacy of constant-load (CL-AEx) and graded aerobic exercise (G-AEx) protocols on cardiorespiratory fitness and functional capability in pediatric survivors of ALL. Methods: Seventy-two pediatric ALL survivors were allocated to CL-AEx, G-AEx, or a control group. Cardiopulmonary fitness [peak oxygen consumption (peak VO₂), peak minute ventilation (VE), ventilatory equivalent for oxygen (VE/VO₂), respiratory exchange ratio (RER), peak oxygen pulse (peak O₂P), maximum heart rate (max HR), and one-minute heart rate recovery (HHR₁)] and functional performance [six-minute walk test (6MWT), 4x10-m shuttle run test (4x10-mSRT), and timed up down stairs (TUDS)] were assessed at pre- and post-intervention. Results: The G-AEx group exhibited significantly enhanced cardiorespiratory and functional outcomes compared to both the CL-AEx and control groups (all p < 0.05). The G-AEx group demonstrated more pronounced improvements, showing significant increases in peak VO₂, VE, VE/VO₂, peak O₂P, and HHR1, alongside a more efficient RER. Functionally, the G-AEx intervention led to superior improvements in 6MWT distance, and significantly faster completion times in the 4x10-mSRT and TUDS, highlighting multi-domain functional gain. Conclusions: In pediatric survivors of ALL, G-AEx demonstrated superior improvements in cardiorespiratory fitness and functional performance compared to CL-AEx over 12 weeks. These findings suggest that G-AEx is an effective modality for addressing acute physical deconditioning in this population. Incorporating G-AEx into clinical rehabilitation may enhance immediate physiological and functional recovery during the survivorship phase. Full article

Background/Objectives: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms may influence folate metabolism and DNA synthesis, potentially affecting disease characteristics and clinical outcomes in hematologic malignancies. This study investigated the associations of MTHFR C677T and A1298C polymorphisms with clinical features and survival outcomes in adult patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). Methods: A total of 92 adult patients with ALL or NHL treated with standard chemotherapy were retrospectively analyzed. MTHFR C677T and A1298C genotypes were determined using real-time polymerase chain reaction. Associations between genotypes and baseline clinical features, treatment response, toxicity, overall survival (OS), and progression-free survival (PFS) were examined. Results: The C677T heterozygous genotype was significantly associated with the presence of B symptoms (p = 0.027). No significant differences were observed across genotypes with respect to other baseline clinical features, treatment response, or treatment-related toxicity. In the overall cohort (ALL + NHL), OS and PFS did not differ significantly by C677T or A1298C genotypes. However, in the NHL cohort, carriers of the C677T variant demonstrated significantly shorter PFS (p = 0.048) and a non-significant trend toward lower OS. This association was also observed in the DLBCL subgroup for PFS (p = 0.043), with a similar non-significant trend observed for OS. Conclusions: Although MTHFR genotyping appears to have limited value for broad clinical stratification, the observed association between the C677T polymorphism and PFS in NHL—particularly in the DLBCL subgroup—suggests a potential subtype-specific relevance that warrants further validation in larger, disease-specific cohorts. Full article

Objective: This study aimed to investigate erythrocyte morphological alterations in hematological malignancies, with particular emphasis on structural differences among leukemia subtypes and anemia. Materials and Methods: Peripheral blood samples were obtained from 60 patients, including individuals with anemia (n = 10), acute lymphoblastic leukemia (ALL, n = 15), acute myeloid leukemia (AML, n = 15), chronic lymphocytic leukemia (CLL, n = 15), and chronic myeloid leukemia (CML, n = 5), as well as 10 healthy controls. Erythrocyte morphology was evaluated using light microscopy and scanning electron microscopy. Morphological abnormalities, including loss of biconcavity, poikilocytosis, echinocyte transformation, burr cells, and stomatocytes, were assessed in accordance with International Council for Standardization in Haematology (ICSH)-based morphological definitions. Results: Distinct erythrocyte morphological alterations were observed across disease groups. AML cases demonstrated pronounced central depression-like or perforation-like structures and hypochromasia. Lymphoid malignancies, particularly ALL and CLL, exhibited increased echinocyte formation, whereas chronic leukemias showed a higher prevalence of stomatocytes and cup-shaped cells. Quantitative scoring indicated that loss of biconcavity was most prominent in anemia, followed by AML, CML, ALL, and CLL. Poikilocytosis was most frequent in anemia, followed by ALL, CLL, AML, and CML. Conclusions: The findings indicate that erythrocyte shape alterations are more heterogeneous and prominent in lymphoid leukemias, whereas myeloid leukemias exhibit distinct ultrastructural membrane abnormalities. Although studies focusing on erythrocyte morphology in leukemia remain limited, the present results provide a foundational morphological reference dataset that may support the development and validation of artificial intelligence-based diagnostic approaches. Further studies involving larger cohorts and expanded imaging analyses are warranted to improve diagnostic accuracy and translational applicability. Full article

Two accelerated magnetic resonance imaging (MRI) protocols for pediatric brain imaging, GOBrain and Deep Resolve Swift Brain, developed by Siemens Healthineers (Erlangen, Germany), were evaluated in a series of clinically relevant pediatric cases at 3 Tesla. Pediatric patients are particularly prone to motion, may be uncooperative, and often require sedation, especially in emergency settings. Consequently, there is a persistent clinical demand for fast brain MRI protocols that provide diagnostically sufficient image quality while minimizing examination time. Contemporary turbo spin-echo (TSE)-based clinical protocols commonly integrate parallel imaging (PI) and simultaneous multi-slice (SMS) techniques to achieve substantial reductions in scan time. Recent advances in three-dimensional volumetric encoding, compressed sensing, and deep learning (DL)-based reconstruction have further mitigated geometry-factor-related noise amplification, enabling higher acceleration factors (GOBrain). In parallel, echo-planar imaging (EPI) has emerged as a promising approach for ultrafast multi-contrast imaging. To overcome the limitations of single-shot EPI, a multi-shot EPI-based brain MRI protocol combined with the DL-based reconstruction method Deep Resolve Swift Brain has been developed. This approach leverages the efficiency of EPI while improving image quality. Using these accelerated protocols, a comprehensive diagnostic multi-contrast brain MRI examination, particularly suited to triage and emergency imaging, can be completed in minutes. This case overview, including therapy-related leukencephalopathy in acute lymphoblastic leukemia (ALL), a brain abscess, traumatic diffuse axonal injury (DAI), a posterior circulation infarction due to vertebral artery dissection, leuokostasis syndrome, and a posterior fossa tumor with obstructive hydrocephalus, demonstrates the potential clinical feasibility of both protocols in pediatric neuroimaging. Both protocols position them as supplementary options alongside established imaging protocols, while dedicated high-resolution protocols might remain necessary for subtle pathological findings, such as focal cortical dysplasia, and for neuronavigation until larger comparative studies are available. Full article

Environmental pollutants are persistent chemicals that pose substantial risks to human health, contributing to global mortality and economic burden. In real-world situations, exposure rarely occurs to single compounds; instead, people are chronically exposed to complex mixtures at low concentrations. However, most regulatory frameworks still rely on single-substance risk assessments, potentially underestimating the hazards associated with combined exposures. This study investigated the cytotoxic interactions of binary mixtures of five environmentally relevant pollutants: bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE), dibutyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), and perfluorooctanoic acid (PFOA), using the human lymphoblast cell line NALM-6. Cells were exposed for 72 h to each compound individually and to all possible binary combinations, reflecting concentrations reported in human plasma or serum. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and interactions were analyzed using the Bliss model of independence and two-way analysis of variance (ANOVA). Intracellular reactive oxygen species were measured using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) probe to explore the involvement of oxidative stress. Synergistic interactions were observed under specific conditions, although not all statistically identified interactions corresponded to biologically significant effects. The BPA-DBP combination produced the highest cytotoxicity when both pollutants were present at 100 nM (31%), consistent with a strong synergistic effect. A similar pattern was observed for BADGE-BPA. ROS production was partially associated with cytotoxicity in these selected mixtures. Overall, these findings highlight the importance of distinguishing statistical synergy from toxicological relevance. Full article