Результаты поиска

Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML.

Leukemic stem cells (LSCs) isolated from acute myeloid leukemia (AML) patients are more sensitive to nuclear factor κB (NF-κB) inhibition-induced cell death when compared with hematopoietic stem and progenitor cells (HSPCs) in in vitro culture. However, inadequate anti-leukemic activity of NF-κB inhibition in vivo suggests the presence of additional survival/proliferative signals that can compensate for NF-κB inhibition. AML subtypes M3, M4, and M5 cells produce endogenous tumor necrosis factor α (TNF). Although stimulating HSPC with TNF promotes necroptosis and apoptosis, similar treatment wi

Emerging Immunotherapy for Acute Myeloid Leukemia.

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward.

Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life

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… The results of this study demonstrated that ssCAR-T-19s can migrate into the CNS and reduce brain leukemic infiltration and significantly eradicate leukemic blasts in the cerebrospinal fluid (CSF) with mildly elevated cytokine levels and only grade 1 CRS ( 71 ). …

Acute Myeloid Leukaemia in Its Niche: the Bone Marrow Microenvironment in Acute Myeloid Leukaemia.

Purpose of reviewAcute myeloid leukaemia (AML) is a heterogeneous malignancy for which treatment options remain suboptimal. It is clear that a greater understanding of the biology of the AML niche will enable new therapeutic strategies to be developed in order to improve treatment outcomes for patients.Recent findingsRecent evidence has highlighted the importance of the bone marrow microenvironment in protecting leukaemia cells, and in particular leukaemic stem cells from chemotherapy-induced cell death. This includes mesenchymal stem cells supporting growth and preventing apoptosis, and alter

Prognostic utility of macrophage polarization (CD68/CD163 ratio) in Egyptian JAK2 positive myeloproliferative neoplasm patients: a single center study.

BackgroundMyeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders with variable clinical outcomes influenced by the bone marrow microenvironment. Tumor-associated macrophages (TAMs), particularly the M1 (CD68⁺) and M2 (CD163⁺) subtypes, play critical roles in inflammation, fibrosis, and immune modulation. This study evaluates CD68- and CD163-positive macrophage frequencies across MPN subtypes and their clinical/prognostic significance.MethodsIn this retrospective cohort study, 121 patients with histopathologically confirmed BCR::ABL1-negative, JAK2V617F-positive MPNs were assess

Prospects of Chimeric Antigen Receptor T-Cell Therapy in Myelofibrosis: From Immunopathogenesis to Therapeutic Strategies.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal hematopoietic dysregulation, amplification of chronic inflammation, and progressive remodeling of the bone marrow fibrotic niche, clinically manifesting as bone marrow failure, splenomegaly, and systemic inflammatory symptoms. Although Janus kinase (JAK) inhibitors can alleviate symptom burden and reduce spleen size, they have limited capacity to eradicate malignant clones or reverse fibrosis. Allogeneic hematopoietic stem cell transplantation remains the only potentially curative option; however, its application is co

Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in recent years as key regulators of the tumor microenvironment. Indeed, they are now considered active players in the pathophysiology of hematologic malignancies rather than passive bystanders in the hematopoietic microenvironment. Onc

Exploring G Protein-Coupled Receptors in Hematological Cancers.

Hematological cancers, such as lymphomas and leukemias, pose significant challenges in oncology, necessitating a deeper understanding of their molecular landscape to enhance therapeutic strategies. This article critically examines and discusses recent research on the roles of G protein-coupled receptors (GPCRs) in myeloma, lymphomas, and leukemias with a particular focus on pediatric acute lymphoblastic (lymphocytic) leukemia (ALL). By utilizing RNA sequencing (RNA-seq), we analyzed GPCR expression patterns in pediatric ALL samples (aged 3-12 years old), with a further focus on Class A orphan

The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers.

Purpose of reviewWe aim to review the most recent findings in the use of NK cells in childhood cancers.Recent findingsNatural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less li

Тригеминальный контакт с артерией у людей, не имеющих тригеминиальной нейронгии - исследование MR.

Основная цель этого исследования состоит в том, чтобы предложить новую нервную сеть, названную BrainNeXt, для автоматизированного обнаружения расстройств мозга с использованием изображений магнитного резонанса (MRI). Кроме того, мы намерены изучить функционирование нашей предлагаемой сети по различным видам медицинского применения. Для обеспечения эффективности классификации изображений с высоким/громким изображением мы собрали новый набор данных МРТ, принадлежащих four Классы:1Болезнь Альцгеймера,2) хроническая ишемия,3) множественный склероз и ()4) контроль. Вдохновленные ConvNeXt, мы спроек

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusi

A Role for Lipid Mediators in Acute Myeloid Leukemia.

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown

Hematopoietic Tumors

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CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic acti

Acute subdural hematoma due to acute myeloid leukemia and B-cell lymphoma.

Chloroma, is an rare malignant tumor characterized by the extramedullary blast proliferation of myeloid lineages that subsequently change the normal architecture of surrounding tissues. Because this is very rare disease, primary central nervous system myeloid sarcoma has not been widely reported. Myeloid sarcoma, as a group of heterogenetic diseases, presents with differential clinical and histological pictures depending upon the primary affected site. We are presenting a 77-year-old gentleman, with past medical history of chronic lymphoblastic leukemia that was not on any treatment and who pr

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… Symptomatic leukemic infiltration of the brain in CLL occurs rarely [ 20 ]. …

Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in hematologic diseases by modulating immune responses, supporting hematopoiesis, and remodeling the bone marrow microenvironment. Clinically, MSCs have been explored for graft-versus-host disease and hematopoietic stem cell transplantation support, while their applications in hematologic malignancies, including acute myeloid leukemia, multiple myeloma, and myelodysplastic syndromes, remain under investigation. However, therapeutic heterogeneity, safety concerns, and standardization challenges limit their clinical transla

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… However, mitochondrial transfer between MSCs and hematopoietic stem and progenitor cells (HSPCs) primarily occurs under stress conditions, such as irradiation, chemotherapy, leukemic infiltration, or inflammatory injury. …

Каннабидиол как иммунный модулятор: всеобъемлющий обзор.

Каннабидиол (КБР), непсихоактивный фитоканнабиноид, полученный из сативы Каннабиса, стал многообещающим терапевтическим агентом в силу его разнообразных фармакологических свойств, включая сильные антивоспалительные, нейрозащитные и иммунодуляторные эффекты. КБР модифицирует иммунную реакцию, включая регулирование активности клеток Т, введение апоптоза макрофага, подавление провоспалительных цитокинов и модуляцию сигнальных путей воспаления и иммунной гомеостазии. Был проведен всеобъемлющий поиск литературы с использованием баз данных PubMed, Scopus и Web of Science в целях выявления соответств

Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML).

Despite the availability of an increasing number of targeted therapeutics and wider use of allogeneic hematopoietic stem cell transplantation, many patients with acute myeloid leukemia (AML) ultimately succumb to this disease. Given their remarkable efficacy in B-acute lymphoblastic leukemia and other CD19-expressing B cell malignancies, there is hope adoptive cellular transfer, particularly chimeric antigen receptor (CAR)-modified immune effector cell (IEC) therapies, may afford a novel, potent immune-based approach for the treatment of AML that complements or replaces existing ones and impro

Плазменная лейкемия клеток с участием мягких тканей; сообщение о редком случае.

Плазменная лейкемия (PCL) — редкий агрессивный вариант множественной миеломы. PCL диагностируется в тех случаях, когда клональные плазменные клетки составляют более чем 20 % из общего циркулирующего лейкоцита или когда абсолютное количество плазменных клеток превышает 2 × 109 /Л. Во время диагностирования часто наблюдается эксклюзивное участие, включая эфлуцию полости. Однако использование мягких тканей редко встречается только в тех случаях, когда one опубликован в английской литературе. Мы сообщим: 74-year-old Человек, который в течение нескольких месяцев испытывал постепенное дыхание. Лабор

FOXM1 contributes to treatment failure in acute myeloid leukemia.

Acute myeloid leukemia (AML) patients with NPM1 mutations demonstrate a superior response to standard chemotherapy treatment. Our previous work has shown that these favorable outcomes are linked to the cytoplasmic relocalization and inactivation of FOXM1 driven by mutated NPM1. Here, we went on to confirm the important role of FOXM1 in increased chemoresistance in AML. A multiinstitution retrospective study was conducted to link FOXM1 expression to clinical outcomes in AML. We establish nuclear FOXM1 as an independent clinical predictor of chemotherapeutic resistance in intermediate-risk AML i