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Topic Review
Monoclonal Antibodies for Acute Myeloid Leukemia/Myelodysplastic Syndromes
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. 
  • 962
  • 20 Jul 2022
Topic Review
New treatment strategies for β-thalassemia
Beta-thalassemia (β-thalassemia) is an autosomal recessive inherited disease characterized by decreased production of the β-globin chains of hemoglobin (Hb) A. The normal structure of HbA is two α- and two β-globin chains. Individuals with β-thalassemia are either homozygous or double heterozygotes for mutations in the β-globin gene.
  • 932
  • 13 Jul 2021
Topic Review
Mechanisms of CLL Cell Stimulation via BcR
The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL.
  • 916
  • 01 Dec 2022
Topic Review
Growth Factors Regulation in Angiogenesis
Cardiovascular disease (CVD) remains a major cause of morbidity and mortality all over the world. Angiogenesis is controlled by cell–cell and cell-extracellular matrix (ECM) interactions through crosstalk between vascular endothelial growth factor (VEGF) and Notch signaling mechanisms. 
  • 906
  • 31 May 2023
Topic Review
Hematopoiesis
Hematopoiesis is a stepwise process through which hematopoietic stem cells (HSCs) differentiate to progenitor cells that demonstrate a restricted potential and eventually further differentiate to form all mature blood and immune cells. 
  • 902
  • 07 Sep 2021
Topic Review
Telomerase Reverse Transcriptase in Leukemia
Telomerase reverse transcriptase (TERT) has been established to possess diagnostic value in leukemia as most adult cells do not express high levels of telomerase. Indeed, studies have shown that prognosis is not favorable in patients who have leukemias expressing high levels of telomerase. Recent research has indicated that targeting of this gene is able to control the survival of malignant cells and therefore offers a potential treatment for TERT-dependent leukemias. 
  • 878
  • 04 Aug 2021
Topic Review
Phosphatidylserine
Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane. In many cancer cells, PS externalizes to the outer cell membrane, a process regulated by calcium-dependent flippases and scramblases. Saposin C coupled with dioleoylphosphatidylserine (SapC-DOPS) nanovesicle (BXQ-350) and bavituximab, (Tarvacin, human–mouse chimeric monoclonal antibodies) are cell surface PS-targeting drugs being tested in clinical trial for treating a variety of cancers. Additionally, a number of other PS-selective agents have been used to trigger cytotoxicity in tumor-associated endothelial cells or cancer cells in pre-clinical studies.
  • 870
  • 25 May 2022
Topic Review
The Identity of Thrombosis
Since “two-path unifying theory” of hemostasis was published, it has been confirmed that hemostasis is blood clotting mechanism forming “hemostatic plug” in bleeding from external and internal bodily injury, and is also thrombosis promoting mechanism in intravascular injury by producing “thrombus”.
  • 864
  • 10 Nov 2022
Topic Review
Genesis of Endotheliopathy
Endotheliopathy, according to the “two-activation theory of the endothelium”, is triggered by the activated complement system in critical illnesses, such as sepsis, diabetes and polytrauma, leading to two distinctly different molecular dysfunctions: (1) the activation of the inflammatory pathway due to the release of inflammatory cytokines, such as interleukins, interferons and tumor necrosis factors, and (2) the activation of the microthrombotic pathway due to the exocytosis of hemostatic factors, including ultra-large von Willebrand factor (ULVWF) multimers and FVIII. These lead to inflammation and microthrombogenesis. The former produces inflammatory diseases, and the latter produces endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), which orchestrates not only TTP-like syndrome characterized by the triad of consumptive thrombocytopenia, microangiopathic hemolytic anemia and multiorgan dysfunction syndrome, but also many other endotheliopathic syndromes. The diagnostic features of EA-VMTD are well established now and therapeutic strategies are being formulated. 
  • 856
  • 11 Oct 2022
Topic Review
JAK2 in Myeloproliferative Neoplasms
The discovery of the activating V617F mutation in Janus kinase 2 (JAK2) has been decisive for the understanding of myeloproliferative neoplasms (MPN). Activated JAK2 signaling by JAK2, CALR, and MPL mutations has become a focus for the development of targeted therapies for patients with MPN. JAK2 inhibitors now represent a standard of clinical care for certain forms of MPN and offer important benefits for MPN patients. However, several key aspects remain unsolved regarding the targeted therapy of MPN with JAK2 inhibitors, such as reducing the MPN clone and how to avoid or overcome a loss of response. The current knowledge on the structure and signaling of JAK2 as central elements of MPN pathogenesis and feature benefits and limitations of therapeutic JAK2 targeting in MPN were summarized.
  • 845
  • 01 Mar 2022
Topic Review
Interleukin-7 Signaling in Lymphoid Malignancies
The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphocyte development and homeostasis. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function of the pathway contributes to malignant transformation. It has become increasingly clear that in lymphoid malignancies, especially in T-cell leukemia, many components of the IL-7 signaling pathway carry genetic alterations leading to increased signaling. Moreover, the majority of leukemic cells express the wild type IL-7 receptor and remain dependent on IL-7 signaling for survival, cell cycle progression and proliferation. In this review, we discuss the role of deregulated IL-7-induced JAK-STAT signaling in lymphoid malignancies of T- and B-cell origin.
  • 839
  • 18 May 2021
Topic Review
Platelet Factor 4
Antibodies against platelet factor 4 (PF4), a protein released from alpha-granules of activated platelets, may cause a number of pathophysiological conditions. The most commonly known is heparin-induced thrombocytopenia (HIT), which develops in a small proportion of people treated with the anticoagulant drug heparin.
  • 832
  • 29 Jan 2022
Topic Review
Selenium and Selenocompounds in Lymphoma
 Lymphomas have been increasing at an alarming rate globally and causing deaths worldwide due to the lack of effective therapies. Among different pharmacological agents, selenium (Se) and selenium-related compounds are widely tested and have gained interest as anticancer agents due to their selectivity to cancer and high efficacy for lymphoma treatment over recent decades. Se is a trace non-metallic element identified as an essential micronutrient that mediates a range of biological functions after incorporation into selenoproteins (SePs), and thus affects the overall quality of human health. Specifically, low levels of Se in serum have been linked with aberrant immune functions, cancer, inflammatory diseases, and predictive of worse outcomes in patients with hematological malignancies including lymphoma. Over the past, a number of promising selenium compounds (SeCs) have been developed to mimic and alter the functions of SePs to achieve pharmacological interventions such as anticancer, antioxidant, and anti-inflammatory activities with minimal adverse effects by suitable chemical substitution. 
  • 829
  • 25 Aug 2022
Topic Review
Genetics of Blastic Plasmacytoid Dendritic Cell Neoplasms
Differential diagnosis between Blastic pDC Neoplasm (BPDCN) and Acute Myeloid Leukemia with pDC expansion (pDC-AML) is particularly challenging, and genomic features can help in diagnosis. The genetic landscape of BPDCN is now well-defined, with important updates concerning MYC/MYC rearrangements, but also epigenetic defects and novel concepts in oncogenic and immune pathways.
  • 829
  • 09 Sep 2022
Topic Review
Diffuse Large B-Cell Lymphoma and Its Tumor Microenvironment
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It is a clinically and morphologically heterogeneous entity that has continued to resist complete subtyping. Molecular subtyping efforts emerged in earnest with the advent of gene expression profiling (GEP). This molecular subtyping approach has continued to evolve simultaneously with others including immunohistochemistry and more modern genomic approaches. The veritable explosion of genomic data availability and evolving computational methodologies have provided additional avenues, by which further understanding and subclassification of DBLCLs is possible.
  • 828
  • 23 May 2022
Topic Review
Megakaryocytes
Megakaryocytes (MKs), a kind of functional hematopoietic stem cell, form platelets to maintain platelet balance through cell differentiation and maturation. The incidence of blood diseases such as thrombocytopenia has increased, but these diseases cannot be fundamentally solved.
  • 813
  • 05 May 2023
Topic Review
Paracetamol Intake and Hematologic Malignancies
Hematologic malignancies are a heterogeneous group of diseases of diverse incidence, prognosis, and etiology that cause 1.3 million cases and more than 700,000 deaths every year worldwide. These malignancies show a stable trend in the last decades, but an increased incidence is observed for myeloma in women.
  • 800
  • 21 Jun 2021
Topic Review
Neurotoxicity in Acute Lymphoblastic Leukemia Treatment
Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. 
  • 793
  • 17 May 2022
Topic Review
Immunotherapeutic Approaches for Angioimmunoblastic T-cell Lymphoma
Escaping the immune system is the main characteristic of a tumor cell. In order to limit the anarchic proliferation of cancer cells, chemotherapies are often used in tumors that have no specific treatment yet, such as AITL. These therapies are proposed to limit the proliferation of dividing cells, i.e., healthy cells as well as tumor cells. This explains the poor benefits of such treatment and the major risk of relapse or even the absence of signs of remission. Importantly, targeting a specific cancer cell type without inducing an effect on healthy cells requires an in-depth knowledge of its phenotype and its surface markers, which can serve as an asset for the development of specific therapies, in particular immunotherapies. If some healthy cells are affected, it is called on-target off-target effects because certain cancer epitopes are partially expressed on non-malignant cells. These therapies include, for example, monoclonal antibodies and chimeric antigen receptors. 
  • 793
  • 25 May 2022
Topic Review
Current Advanced on Hematopoietic Stem Cell
Blood is a connective tissue made up of approximately 34% cells and 66% plasma, transporting nutrients, gases and molecules in general to the whole body. Hematopoiesis is the main function of bone marrow. Human hematopoietic stem and progenitor cells reside in the bone marrow microenvironment, making it a hotspot for the development of hematopoietic diseases. Numerous alterations that correspond to disease progression have been identified in the bone marrow stem cell niche. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells determine the balance between the proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation. However, our understanding of human hematopoiesis and the associated niche biology remains limited due to accessibility to human material and the limits of in vitro culture models. Traditional culture systems for human hematopoietic studies lack microenvironment niches, spatial marrow gradients, and dense cellularity, rendering them incapable of effectively translating marrow physiology ex vivo.
  • 790
  • 15 Mar 2022
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