Search Results (980)

(1) Background: Methylobacterium radiotolerans (M. radiotolerans) is a fastidious, aerobic, Gram-negative bacillus primarily found in environmental sources such as soil and sewage, with rare clinical isolation. Its identification remains challenging due to poor growth with conventional culture methods. (2) Case presentation: A 42-year-old male patient with early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) presented with M. radiotolerans bacteremia during hospitalization. The organism was successfully isolated from peripheral blood using the Myco/F Lytic culture vial (Becton, Dickinson and Company, Lincoln, MT, USA). Comparative analysis demonstrated markedly superior growth of M. radiotolerans in Myco/F Lytic culture vials compared with Plus Aerobic/F Lytic and Lytic/10 Anaerobic/F culture vials (Becton, Dickinson and Company, Lincoln, MT, USA). Antimicrobial susceptibility testing, performed with the epsilometer test (E-test) and Bauer–Kirby disk diffusion (BK) method, guided the selection of an appropriate therapeutic regimen. The patient’s infection was ultimately controlled following targeted antimicrobial therapy. (3) Conclusions: M. radiotolerans demonstrates a distinct growth preference for the Myco/F Lytic culture medium. This observation highlights the importance of considering alternative culture media in cases of rare or fastidious bacterial infections that cannot be reliably detected using conventional Plus Aerobic/F Lytic or Lytic/10 Anaerobic/F culture vials, which are typically employed for clinical isolation of aerobic and anaerobic bacteria. Full article

Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway mutations, and ABL-class fusions. Patients with Ph-like ALL typically experience poor outcomes with conventional chemotherapy, underscoring the need for intensified and targeted therapeutic approaches. Methods: This review summarizes current evidence regarding the role of hematopoietic stem cell transplantation (HSCT) in patients with Ph-like ALL. We analyzed retrospective cohort studies, registry data, and ongoing clinical trials, focusing on transplant indications, molecular risk stratification, measurable residual disease (MRD) status, timing of transplant, and post-transplant strategies. Results: Retrospective data suggest that HSCT in first complete remission (CR1) may improve survival in patients with high-risk molecular lesions or MRD positivity at the end of induction. However, the lack of prospective data specific to Ph-like ALL limits definitive conclusions. Post-transplant relapse remains a challenge, and novel strategies, including the use of tyrosine kinase inhibitors or JAK inhibitors as post-HSCT maintenance therapy, are being explored. Emerging immunotherapies, such as chimeric antigen receptor (CAR) T cells, may reshape the therapeutic landscape and potentially alter the indications for transplantation. Conclusions: HSCT remains a crucial therapeutic option for selected patients with Ph-like ALL, particularly those with poor molecular risk features or persistent MRD. However, further prospective studies are needed to evaluate the indication for HSCT in CR1 and the potential integration of transplantation with targeted and immunotherapeutic strategies. Personalized treatment approaches based on genomic profiling and MRD assessment are essential to improve outcomes in this high-risk subset. Full article

Background: Although telomere length maintenance is a common characteristic of hematological malignancies, the role of telomere length as a prognostic factor to stratify acute lymphoblastic leukemia (ALL) patients depending on their risk of relapse remains elusive. Methods: This knowledge gap motivated us to examine telomere length values in children with ALL at the time of diagnosis and after treatment using quantitative polymerase chain reaction (qPCR) (n = 35). To achieve high-resolution precision and cell specificity, a quantitative fluorescence in situ hybridization (qFISH) technique was developed (n = 5). Results: The results demonstrated statistically significant evidence of telomere shortening in the lymphoblasts of children with ALL but not in the lymphocytes of children after remission following treatment. Our findings also suggested a significant association between telomere shortening and a high risk of relapse disease. Last but not least, our preliminary results showed a trend that telomere shortening was more pronounced in children with B-ALL compared to those with T-ALL in a non-significant manner. Conclusions: Consequently, the current study provides preliminary insights into the potentially substantial prognostic value of telomere length in the progression of pediatric ALL, with the possibility of predicting treatment response. To clarify the application of telomere length as a possible biomarker for disease progression and treatment response in children with ALL, the telomere length values of additional participants need to be examined in further studies. Full article

Tyrosine kinase 2 (TYK2) mediates the signaling pathways of proinflammatory cytokines such as interleukin (IL)-12, IL-23, and type I interferons (IFNs) and plays a pivotal role in the pathogenesis of psoriasis and various other immune-mediated diseases. Deucravacitinib, a selective oral TYK2 inhibitor, has been approved for the treatment of psoriasis and demonstrated high efficacy and a favorable safety profile. This review summarizes the potential for expanding deucravacitinib indications based on case reports, clinical trials, and preclinical studies. Diseases in which TYK2 pathway has been demonstrated to be involved and for which clinical benefit of deucravacitinib has been reported include discoid lupus erythematosus, systemic lupus erythematosus, alopecia areata, lichen planus, palmoplantar pustulosis, psoriatic arthritis, systemic sclerosis, interstitial pneumonia, inflammatory bowel disease, and chronic recurrent multifocal osteomyelitis. Furthermore, emerging research suggests potential therapeutic applications in neurodegenerative diseases such as Alzheimer’s disease, and malignancies such as type 1 diabetes, vascular calcification in chronic kidney disease, T-cell acute lymphoblastic leukemia, and multiple sclerosis. Deucravacitinib may exert therapeutic effects by broadly suppressing cytokine signaling in a diverse range of inflammatory disorders. Ongoing clinical trials and mechanistic studies are required to clarify the efficacy and support its future indications. Full article

The agro-industrial sector is a key pillar of the global economy, playing a central role in the supply of food, energy, and industrial inputs. However, its production chain generates significant amounts of residues and by-products, which, if not properly managed, may cause considerable environmental impacts. In this context, the search for alternatives to reuse these materials is essential, particularly when they can be converted into high-value products. One promising application is their use as a nutrient source for microorganisms in high-value biotechnological processes, such as the production of L-Asparaginase, an important enzyme used both in mitigating acrylamide formation in foods and as a biopharmaceutical in Acute Lymphoblastic Leukemia therapy. This approach offers a sustainable and competitive pathway, combining robust, scalable, and economical enzyme production with waste valorization and circular economy benefits. Although interest in developing more sustainable processes is growing, supported by international agreements and strategies for the valorization of agricultural residues, important challenges remain. The variability and impurity of residues pose significant challenges for producing biological products for the pharmaceutical and food industries. In addition, meeting regulatory requirements is essential to ensure product safety and traceability, while achieving high yields is crucial to maintain production viability compared to conventional media. Overcoming these barriers is critical to enable industrial-scale application of this approach. This review provides a residue-centered revision of the most relevant agro-industrial by-products used as substrates for L-asparaginase production, systematically comparing their compositional characteristics, fermentation strategies, and reported yields. Additionally, we present a novel SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis that critically examines the technical, regulatory, and economic challenges of implementing residue-based processes on an industrial scale. Full article

Acute myeloid leukemia (AML), the second most common type of leukemia in children, is a heterogeneous disease known to be caused by genetic, epigenetic, and transcriptional changes, predominantly somatic and germline abnormalities. Despite significant improvement of overall survival rates, the prognosis of pediatric AML remains unfavorable in comparison with acute lymphoblastic leukemia (ALL), especially in relapsed or refractory settings. The current status and future directions are focused on establishing an accurate diagnosis and treatment strategies based on the genomic background. Next-generation sequencing (NGS) technologies enable a broader understanding of the basis of the disease for the purpose of determining pathology-associated mutations and additional prognostic biomarkers in pediatric AML. This review focuses on providing an overview of the known and possible prognostic factors, as well as genetic landscape of pediatric AML patients and how it can be used to accurately differentiate and risk stratify patients. It also presents potential candidate modifications for risk adjustment and targeted therapy. Furthermore, we describe in this article a case of a 22-month-old male patient with relapsed M5 high-risk group (HRG) AML with complex karyotype. Due to belonging to the HRG, as well as unsatisfactory chemotherapy response, the patient underwent matched unrelated donor (MUD) stem cell transplantation (SCT). Full article

Background/Objectives: Malignant neoplasms in children include leukemias. The main types are B-cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). Treatments are expensive, which is a particular problem in low-income countries. The main objective of this work was to develop specific nanosystems with small amounts of drug, allowing for affordable treatments. To this end, we designed ternary gold nanosystems (Au@16-Ph-16/DNA–Dauno) composed of daunomycin, a DNA biopolymer as a stabilizer, and the cationic surfactant gemini (TG) as a compacting agent for the DNA–daunomycin complex. Methods: Fluorescence, UV–visible, and CD spectroscopy, DLS and zeta potential, cell viability assays, TEM, AFM, and confocal microscopy were used to characterize and optimize nanocomposites. Results: The nanoparticles (Au@TG) obtained were small, stable, and highly charged in solution, allowing for optimal absorption and efficacy, capable of inducing the aggregation of the ternary nanosystem upon entering the cell, further enhancing its anticancer effect. Using nanoparticles, treatments can be redirected to the site of action, increasing the solubility and stability of the drug, minimizing the side effects of traditional treatments, and helping to overcome resistance to chemotherapy Conclusions: A significant decrease in the growth of pediatric B-ALL-derived cell lines (SEM and SUP-B15), constituting a potential and more affordable therapy for this type of pathology. Full article

Background: Pediatric sepsis is a life-threatening disease that is associated with the progression of acute lymphoblastic leukemia (ALL) and the recurrence of B-cell ALL (B-ALL). Although previous studies have reported a partial association between sepsis and ALL, there is limited research on the shared genes between pediatric sepsis and relapsed B-ALL. This study aims to further elucidate the more comprehensive and novel common genetic factors and molecular pathways between the two diseases. Methods: Gene expression datasets pertaining to pediatric sepsis (GSE13904, GSE80496) and relapsed B-ALL (GSE3910, GSE28460) were retrieved from the Gene Expression Omnibus database for this retrospective analysis. The initial analysis identified differentially expressed genes common to both pediatric sepsis and relapsed B-ALL. Subsequent investigations employed three complementary approaches: protein–protein interaction networks, molecular complex detection (MCODE) clustering functions, and support vector machine recursive feature elimination model to separately identify the diagnostic biomarkers for each condition. Importantly, key common genes were identified by overlapping the diagnostic genes for pediatric sepsis and relapsed B-ALL. Further characterization involved comprehensive functional analysis through the Metascape platform, construction of transcription factor (TF)-mRNA-microRNA (miRNA) networks, drug prediction, and molecular docking to explore their biological significance and potential therapeutic targets. Results: Comparative analysis of pediatric sepsis-related and relapsed B-ALL-related datasets revealed two shared genetic markers, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9), exhibiting diagnostic significance and consistent upregulation in both disease groups. Transcriptional regulatory network analysis identified specificity protein 1 (SP1) as the principal transcription factor capable of coregulating LTF and MMP9 expression. In addition, molecular docking demonstrated high-affinity interactions between curcumin and MMP9 (−7.18 kcal/mol) as well as reserpine and LTF (−5.4 kcal/mol), suggesting their potential therapeutic utility for clinical evaluation. Conclusions: These findings elucidate the molecular pathogenesis involving LTF and MMP9 in pediatric sepsis and relapsed B-ALL, providing novel insights for clinical diagnosis and therapeutic development. Full article

A three-year-old male bearded dragon (Pogona vitticeps) exhibited acute anorexia. Biochemistry revealed mild hyperproteinemia (88 g/L) and elevated liver enzymes (ALT 60 U/L, AST 272 U/L), while the hematology report showed marked lymphocytosis. The animal had been clinically normal at a routine examination 10 months earlier. Based on the clinical and laboratory findings, acute lymphoblastic leukemia was suspected. Treatment was initiated with methylprednisolone (1 mg/kg PO q24h), marbofloxacin (10 mg/kg IM q24h), and lomustine (80 mg/m² PO q14d), calculated according to reptile-specific body surface area formulas. A transient stabilization was followed by sudden deterioration on day 3, characterized by hematemesis and severe respiratory distress, leading to spontaneous death. A complete necropsy including histopathology and anti-CD3 immunohistochemistry revealed disseminated infiltration of neoplastic T-lymphocytes throughout all major visceral organs and confirmed the diagnosis of T-cell lymphoblastic lymphoma/leukemia (L/L). This case represents a rare report of systemic acute lymphoblastic L/L in a bearded dragon and underlies the importance of comprehensive diagnostics in reptiles with non-specific clinical signs and the challenges in the treatment of neoplastic diseases in exotic species. Full article

Background/Objectives: During cancer development, tumor cells accumulate somatic mutations, which could generate tumor-specific neoantigens. The aberrant protein can be recognized by the immune system as no-self, triggering an immune response against cells expressing this aberrant protein which could mediate tumor control or rejection. Since the expression of this mutated protein is exclusive to tumor cells, great efforts are being made to identify neoantigens of relevance in the development of new cancer treatment strategies. In comparison to adulthood tumors, pediatric malignancies present fewer mutations and thus fewer potential neoantigens. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy worldwide that can be benefited by the identification of neoantigens for immunotherapy approaches, the landscape of neoantigens in ALL is not well known, therefore the aim of our study was to identify potential neoantigens in ALL pediatric patients. Methods: To identify neoantigens in ALL, whole-exome sequencing of matched tumor-normal cells from pediatric cases was performed, with these data HLA-I alleles predicted and somatic mutations identified to propose potential neoantigens based on binding affinity of mutated peptide-HLA-I. Results: We found a strong correlation between tumor mutational burden (TMB) and neoantigen load (p < 0.001) but no correlation with prognosis. Furthermore, TMB and neoantigens were greater in ALL patients with at least one mutated DNA mismatch repair gene (p < 0.001). Also, differences between B- and T-cell ALL were found but statistical significance did not remain after permutation. Conclusions: The presence of neoantigens in pediatric cases with ALL makes the neoantigen-based immunotherapy a promising new strategy for the treatment of this malignancy, especially for patients with relapse. Full article

Asparaginase (ASNase) is an important enzyme used to treat acute lymphoblastic leukemia. However, the clinical use of the currently available ASNases is limited because of their associated side effects. One of the major reasons for these adverse effects is the coactivity of glutaminase (GLNase) with ASNase. Furthermore, the concomitant urease activity may exacerbate the toxicity associated with ASNase treatment. Therefore, identifying novel sources of ASNase with minimal or no glutaminase and urease activities is important. We isolated a marine fungal strain, MABIK FU00000820, which produced ASNase free of GLNase and urease activity. Based on morphological and phylogenetic analyses, this strain was identified as Paraconiothyrium cyclothyrioides. The crude extract of intracellular ASNase exhibited the maximum activity at 37–50 °C, pH 8.5, and 0% (w/v) NaCl. In addition, the enzyme stability assay showed that the P. cyclothyrioides ASNase pre-treated at 4–25 °C for 2 h retained 77% of its activity compared to the untreated control. Based on the available literature, this appears to be the first study to investigate ASNase from P. cyclothyrioides, and it is of particular significance because the enzyme exhibits neither GLNase nor urease activity. Full article

Systemic viral infections are frequently life-threatening in immunocompromised children. Many viral pathogens are reported to be the cause of morbidity and mortality in these pediatric patients, but scarce evidence is related to respiratory syncytial virus infection (RSV), which is one of the main viral causes of lower respiratory tract infection in infants and young children. Herein we report the experience of the Center of Pediatric Hematology Oncology of Catania regarding RSV infection in pediatric leukemia patients, describing four cases: three with only respiratory involvement and complete recovery (two of them presented mild symptoms and one evolved into severe respiratory failure) and a fourth case with an initial hepatic and pulmonary involvement leading to death. Unfortunately, some viral infections have delayed diagnoses because of lack of awareness and atypical presentation. Therefore, our intent is to highlight the importance of mindfulness of the occurrence of this infection and of its typical and atypical manifestations in order to detect it early and decrease the risk of morbidity and mortality. Full article

CAR-T therapy has transformed the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), particularly in pediatric and young adult patients. Many studies report one-year overall survival rates of between 60% and 80% following therapy. Event-free survival rates at one year are around 50–70%, with 40–50% of patients in remission after two years. Despite these impressive results, disease relapse remains a problem. Future CAR-T cell platforms should target multiple antigens, and the optimal design of such constructs must be determined. Modern trials should explore the role of CAR-T cell therapy as a consolidation treatment for patients with high-risk ALL, including those with persistent minimal residual disease at the end of induction/consolidation therapy, an IKZF1-positive gene expression profile, or a TP53 mutation or Ph-like gene expression profile. Improving the efficiency of gene-editing methods could lead to higher success rates in creating CAR-T cells, as well as reducing manufacturing time and costs. Producing universal CAR-T cells from healthy donors could significantly reduce production time and costs. These issues underscore the dynamic and evolving nature of B-ALL research. Ongoing studies and clinical trials are addressing many of these challenges in order to improve outcomes for B-ALL patients and expand the applications of CAR-T cell therapy. Full article

Background/Objectives: Adult acute lymphoblastic leukemia (ALL) often has poor outcomes, especially after relapse or treatment failure. Many patients eventually become ineligible for curative treatment and require only supportive care or low-intensity chemotherapy. However, data on prognosis and predictive factors in this context are limited. The study aim was to evaluate survival and identify prognostic factors in patients with relapsed/refractory ALL receiving supportive care. Methods: We conducted a retrospective observational study of 59 patients at two tertiary hospitals in Mexico. All patients had exhausted curative treatment options. Clinical variables at diagnosis and relapse were analyzed, including age, leukocyte counts, relapse timing, prior treatment lines, transfusion needs, and use of prognostic scores. Kaplan–Meier analysis was used to estimate survival, and multivariate models were applied to identify predictors of overall survival. Results: Fifty-nine patients were included (median age 31 years, balanced gender). Most received two prior high-intensity chemotherapy lines. Median overall survival was 137 days, with transfusion requirements being the only significant prognostic factor; neither the Palliative Prognostic Index nor the Charlson Comorbidity Index demonstrated predictive value. Conclusions: In patients with relapsed/refractory ALL managed with supportive care, survival remains limited. Transfusion dependence is a strong adverse prognostic factor, likely reflecting disease burden and logistical barriers to outpatient care. These findings highlight the need for earlier integration of palliative care and the development of tailored prognostic tools for this population. Full article

In the last few decades, chimeric antigen receptor (CAR) T-cell therapy has led to a paradigm shift in the treatment of hematological malignancies, including various subtypes of B-cell non-Hodgkin’s lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. However, most patients experience refractoriness to CAR T-cells or relapse after treatment. Many efforts are underway to understand the mechanisms behind CAR T-cell failure, which are mainly related to CAR T-cell dysfunction, tumor-intrinsic resistance, an immunosuppressive tumor microenvironment, manufacturing issues, or patient-related factors. Several strategies are being developed to overcome these resistance mechanisms, including the engineering of more functional allogeneic CAR T-cell products, the targeting of alternative tumor antigens, and combination therapies with other drugs such as checkpoint inhibitors or small molecules to enhance CAR T-cell efficacy. In this review, we will provide an updated overview of the mechanisms of CAR T-cell failure and the therapeutic advances currently under development to address them. Full article