Advancing Chimeric Antigen Receptor T-Cell Therapy for Acute Myeloid Leukemia: Current Limitations and Emerging Strategies.

Chimeric antigen receptor (CAR) T-cell therapy represents one of the most impressive advances in anticancer therapy of the last decade. While CAR T-cells are gaining ground in various B cell malignancies, their use in acute myeloid leukemia (AML) remains limited, and no CAR-T product has yet received approval for AML. The main limitation of CAR-T therapy in AML is the lack of specific antigens that are expressed in leukemic cells but not in their healthy counterparts, such as hematopoietic stem cells (HSCs), as their targeting would result in an on-target/off-tumor toxicity.

Dapagliflozin ameliorates Lafora disease phenotype in a zebrafish model.

Lafora disease (LD) is an ultra-rare and still incurable neurodegenerative condition. Although several therapeutic strategies are being explored, including gene therapy, there are currently no treatments that can alleviate the course of the disease and slow its progression. Recently, gliflozins, a series of SGLT2 transporter inhibitors approved for use in type 2 diabetes mellitus, heart failure and chronic kidney disease, have been proposed as possible repositioning drugs for the treatment of LD.

Impact of non-weight-dependent low-dose somatropin on bone accrual in childhood-onset GH deficient in the transition: an 18-month randomized controlled trial.

Objective: Discontinuation of growth hormone therapy (rhGH) upon completion of linear growth may adversely affect bone mineral density and content (BMD/BMC) in adolescents with childhood-onset GH deficiency (CO-GHD) and predisposition to osteoporosis. Although the benefits of weight-dependent somatropin high doses over bone gain are established, little is known about fixed low doses. We analyzed the impact of non-weight-based low-dose somatropin on bone accrual during the transition among CO-DGH patients, treated since childhood.

mutation-related immune checkpoint molecule absent in melanoma 2 () contributes to immune infiltration in pediatric and adult acute myeloid leukemia: evidence from bioinformatics analysis.

Background: The use of FMS-like tyrosine kinase 3 () as a crucial target for kinase inhibitors is well established, but its association with immune infiltration remains unclear. This study aimed to explore the relationship between mutations and immune checkpoint molecules (ICMs) in patients with acute myeloid leukemia (AML).

Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify the ICMs associated with mutations.

Perioperative and long-term outcomes of bilateral cardiac sympathetic denervation via video-assisted thoracoscopic surgery in patients with refractory ventricular arrhythmias.

Background: Bilateral cardiac sympathetic denervation (CSD) performed via video-assisted thoracoscopic (VAT) surgery shows potential in managing ventricular tachycardia (VT), thereby reducing arrhythmic burden. In this setting, the scarcity of studies addressing both perioperative and long-term outcomes creates a substantial gap in the optimal management of patients with multiple comorbidities and limited treatment options. This observational study aimed to assess the medical comorbidities, as well as the short- and long-term outcomes of patients who underwent CSD for VT refractory to catheter ablation and medical therapy at a referral tertiary teaching hospital.

Prognostic Significance of Tumor-Stroma Ratio (TSR) in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

The management of head and neck squamous cell carcinoma (HNSCC) relies heavily on TNM staging and WHO histologic grading; however, in recent years, the analysis of prognostic markers expressed in the tumor stroma has gained attention. The tumor-stroma ratio (TSR) quantifies the proportion of tumor tissue relative to the surrounding stromal tissue; it is assessed with the percentage of stromal tissue within the tumor area, with a cutoff point of 50% being widely used to discriminate high-stroma cancer. In this systematic review and meta-analysis, we investigated the potential prognostic role of the TSR in HNSCC.

Generation and Characterization of hiPS Lines from Three Patients Affected by Different Forms of -Related Neurological Disorders.

Hereditary spastic paraplegias are rare genetic disorders characterized by corticospinal tract impairment. Spastic paraplegia 83 (SPG83) is associated with biallelic mutations in the gene, leading to varied severities from neonatal to juvenile onset. The function of HPDL is unclear, though it is speculated to play a role in alternative coenzyme Q10 biosynthesis.

Comparative efficacy and safety of first-line tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and network meta-analysis.

Background: Tyrosine kinase inhibitors (TKIs) have become the preferred drugs for the treatment of chronic phase (CP) chronic myeloid leukemia (CML). This study aims to compare the safety and efficacy of different TKIs as first-line treatments for CML using network meta-analysis (NMA), providing a basis for the precise clinical use of TKIs.

Methods: A systematic search was conducted on PubMed, Cochrane Library, Embase, China National knowledge Infrastructure (CNKI), Wanfang, Chinese Science and Technology Periodical Databases (VIP), SinoMed and ClinicalTrials.

Puberty in girls with Prader-Willi syndrome: cohort evaluation and clinical recommendations in a Latin American tertiary center.

Introduction: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age.

CAR-T Cells in Acute Myeloid Leukemia: Where Do We Stand?

Despite recent advances, the prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to disease recurrence and the development of resistance to both conventional and novel therapies. Engineered T cells expressing chimeric antigen receptors (CARs) on their cellular surface represent one of the most promising anticancer agents. CAR-T cells are increasingly used in patients with B cell malignancies, with remarkable clinical results despite some immune-related toxicities.

Generation of a human induced pluripotent stem cell line (FSMi001-A) from fibroblasts of a patient carrying heterozygous mutation in the REEP1 gene.

Hereditary spastic paraplegias (HSPs) a group of rare, clinically, and genetically heterogeneous disorders characterized by progressive degeneration of the corticospinal tract. Among these HSPs, SPG31 is due to autosomal dominant mutations in the receptor expression-enhancing protein 1 (REEP1) gene. Over 80 genes have been associated with HSPs, and the list is constantly growing as research progresses.

Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.

Hereditary spastic paraplegias (HSPs) comprise a family of degenerative diseases mostly hitting descending axons of corticospinal neurons. Depending on the gene and mutation involved, the disease could present as a pure form with limb spasticity, or a complex form associated with cerebellar and/or cortical signs such as ataxia, dysarthria, epilepsy, and intellectual disability. The progressive nature of HSPs invariably leads patients to require walking canes or wheelchairs over time.

ATP-Binding Cassette Subfamily G Member 2 in Acute Myeloid Leukemia: A New Molecular Target?

Despite the progress in the knowledge of disease pathogenesis and the identification of many molecular markers as potential targets of new therapies, the cure of acute myeloid leukemia remains challenging. Disease recurrence after an initial response and the development of resistance to old and new therapies account for the poor survival rate and still make allogeneic stem cell transplantation the only curative option. Multidrug resistance (MDR) is a multifactorial phenomenon resulting from host-related characteristics and leukemia factors.

Correlation between IPSET-t risk at diagnosis and subsequent hemorrhage in patients with essential thrombocythemia; a single institution experience.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased risk of thrombotic and hemorrhagic events, that represent the leading causes of mortality and morbidity. Currently, while thrombotic risk is assessed through the IPSET-t and r-IPSET scores, there is no specific prognostic tool used to predict hemorrhagic risk in ET. The aim of the study was to define incidence and risk factors connected to hemorrhagic events by retrospectively analyzing 308 ET patients diagnosed between 1996 and 2022 at the Division of Hematology of Udine and treated according to the current international guidelines.

Azimuthal Correlations within Exclusive Dijets with Large Momentum Transfer in Photon-Lead Collisions.

The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization.

LINE-1 regulates cortical development by acting as long non-coding RNAs.

Long Interspersed Nuclear Elements-1s (L1s) are transposable elements that constitute most of the genome's transcriptional output yet have still largely unknown functions. Here we show that L1s are required for proper mouse brain corticogenesis operating as regulatory long non-coding RNAs. They contribute to the regulation of the balance between neuronal progenitors and differentiation, the migration of post-mitotic neurons and the proportions of different cell types.

B-cell prolymphocytic leukemia with P53 abnormalities successfully treated with bendamustine and rituximab: a report of three cases.

Background: B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell tumor with an aggressive clinical course and poor prognosis. It is characterized by prominent splenomegaly and prolymphocytes exceeding 55% of the lymphoid cells in the blood. Purine analog-based chemo-immunotherapy is the first-line therapy for B-PLL.

Checkpoint Inhibitors in Acute Myeloid Leukemia.

The prognosis of acute myeloid leukemia (AML) remains unsatisfactory. Among the reasons for the poor response to therapy and high incidence of relapse, there is tumor cell immune escape, as AML blasts can negatively influence various components of the immune system, mostly weakening T-cells. Since leukemic cells can dysregulate immune checkpoints (ICs), receptor-based signal transductors that lead to the negative regulation of T-cells and, eventually, to immune surveillance escape, the inhibition of ICs is a promising therapeutic strategy and has led to the development of so-called immune checkpoint inhibitors (ICIs).

ABCG2 in Acute Myeloid Leukemia: Old and New Perspectives.

Despite recent advances, prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to poor response to therapy or relapse. Among causes of resistance, over-expression of multidrug resistance (MDR) proteins represents a pivotal mechanism. ABCG2 is an efflux transporter responsible for inducing MDR in leukemic cells; through its ability to extrude many antineoplastic drugs, it leads to AML resistance and/or relapse, even if conflicting data have been reported to date.

Present and Future Role of Immune Targets in Acute Myeloid Leukemia.

It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets and effectors of this immune-based therapy could be monoclonal antibodies directed against LSC antigens such as CD33, CD123, and CLL-1 (either as direct targets or via several bispecific T-cell engagers), immune checkpoint inhibitors acting on different co-inhibitory axes (alone or in combination with conventional AML drugs), and novel cellular therapies such as chimeric antigen receptor (CAR) T-cells designed against AML-specific antigens.