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Topic Review
The Nephrotoxicity of Drugs
A dynamic development of oncology has been observed, resulting from the increasingly frequent occurrence of neoplasms and therefore, increasing population of patients. The most effective form of therapy for cancer patients is complex multidisciplinary specialized disease management, including nephro-oncology care. Different forms of renal function impairment are frequently diagnosed in cancer patients.
  • 1.4K
  • 26 Dec 2022
Topic Review
Multiple Myeloma Pathogenesis and The Existing Therapies
Multiple myeloma (MM) is a mature B-cell neoplasm that is characterized by uncontrolled growth of plasma cells (PCs) in bone marrow (BM) which leads to excessive secretion of antibodies. The progression of MM is a multistep process that starts with an asymptomatic premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS), in which BM produces abnormal PCs and secretes M protein instead of normal antibodies.
  • 1.4K
  • 17 Mar 2023
Topic Review
Measurable Residual Disease in AML
Relapse is still a major problem in AML because it occurs in about 60–80% of patients, even those who have previously achieved complete remission (CR), defined by the presence of ≤5% bone marrow (BM) leukemic cells. Thus, since CR is unable to predict the relapse risk, significantly more sensitive techniques aimed at identifying AML cells in BM or peripheral blood, a parameter termed measurable residual disease (MRD), have been developed. Among them, RT-qPCR, which analyses appropriate molecular markers, and multiparameter flow cytometry (MFC), which analyses aberrantly expressed antigens, have been identified as the methods of choice for MRD detection. 
  • 1.4K
  • 22 Sep 2021
Topic Review
Pediatric Mixed-Phenotype Acute Leukemia
Mixed phenotypic acute leukemias (MPAL) are rare hematological malignancies in children, accounting for less than 5% of pediatric acute leukemias. MPAL are heterogeneous and can exhibit cross-lineage myeloid, B-lymphoid, or T-lymphoid antigen expression on a single blast population (biphenotypic) or have distinct single-lineage blast populations (bilineal). Due to phenotypic and genetic diversity, lack of well-defined diagnostic criteria, treatment resistance, and lineage switch, MPAL often present a diagnostic dilemma, and prove difficult to treat.
  • 1.3K
  • 30 Nov 2021
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.
  • 1.3K
  • 15 Mar 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. 
  • 1.3K
  • 11 Oct 2022
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. 
  • 1.3K
  • 04 Aug 2021
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. 
  • 1.3K
  • 25 Aug 2022
Topic Review
Prognosis in Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic neoplasms characterized by ineffective hematopoiesis and myelodysplasia with a variable spectrum of clinical–biological features that can be used to build a prognostic estimation. 
  • 1.3K
  • 27 May 2021
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.
  • 1.2K
  • 09 Sep 2022
Topic Review
Dasatinib-Mediated Immunomodulatory Effects in Chronic Myeloid Leukemia
Tyrosine kinase inhibitors (TKIs) have been extensively used as a treatment for chronic myeloid leukemia (CML). Dasatinib is a broad-spectrum TKI with off-target effects that give it an immunomodulatory capacity resulting in increased innate immune responses against cancerous cells and viral infected cells.
  • 1.2K
  • 15 Mar 2023
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.
  • 1.2K
  • 01 Mar 2022
Topic Review
Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy
Single-targeted chimeric antigen receptor (CAR) T cells tremendously improve outcomes for patients with relapsed/refractory hematological malignancies and are considered a breakthrough therapy. However, over half of treated patients experience relapse or refractory disease, with antigen escape being one of the main contributing mechanisms. Dual-targeting CAR T-cell therapy is being developed to minimize the risk of relapse or refractory disease. Preclinical and clinical data on five categories of dual-targeting CAR T-cell therapies and approximately fifty studies were summarized to offer insights and support the development of dual-targeting CAR T-cell therapy for hematological malignancies. The clinical efficacy (durability and survival) is validated and the safety profiles of dual-targeting CAR T-cell therapy are acceptable, although there is still room for improvement in the bispecific CAR structure. It is one of the best approaches to optimize the bispecific CAR structure by boosting T-cell transduction efficiency and leveraging evidence from preclinical activity and clinical efficacy.
  • 1.2K
  • 01 Aug 2022
Topic Review
Novel Treatment Options for Childhood Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia is the most common blood cancer in pediatric patients. Despite the enormous progress in ALL treatment, which is reflected by a high 5-year overall survival rate that reaches up to 96% in the most recent studies, there are still patients that cannot be saved. Treatment of ALL is based on conventional methods, including chemotherapy and radiotherapy. These methods carry with them the risk of very high toxicities. Severe complications related to conventional therapies decrease their effectiveness and can sometimes lead to death. Therefore, currently, numerous studies are being carried out on novel forms of treatment.
  • 1.2K
  • 21 Apr 2022
Topic Review
The Place of Splenectomy in Autoimmune Hemolytic Anemia
Autoimmune hemolytic anemia (AIHA) is a rare, very heterogeneous, and sometimes life-threatening acquired hematologic disease characterized by increased red blood cell (RBC) destruction by autoantibodies (autoAbs), either with or without complement involvement.  AIHA can be primary (idiopathic) but is more often secondary, triggered by infections or drug use or as a part of other diseases. As the location of origin of autoAbs and the location of autoAb-mediated RBC clearance, as well as the location of extramedullary hematopoiesis, the spleen is crucially involved in all the steps of AIHA pathobiology. Splenectomy, which was the established second-line therapeutic option in corticosteroid-resistant AIHA patients for decades, has become less common due to increasing knowledge of immunopathogenesis and the introduction of targeted therapy. 
  • 1.2K
  • 11 Sep 2023
Topic Review
Molecular Basis of FIX Deficiency in Hemophilia B
Hemophilia is an X-linked recessive bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII) or factor IX (FIX), which are named hemophilia A (OMIM#306700) and hemophilia B (OMIM#306900), respectively. Coagulation factor IX (FIX) is a vitamin K dependent protein and its deficiency causes hemophilia B, an X-linked recessive bleeding disorder. More than 1000 mutations in the F9 gene have been identified in hemophilia B patients. Hemophilia is an X-linked recessive bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII) or factor IX (FIX), which are named hemophilia A (OMIM#306700) and hemophilia B (OMIM#306900), respectively. Because the genes of FVIII and FIX are located in chromosome X, hemophilia has historically been considered as a “male disease".
  • 1.2K
  • 25 Mar 2022
Topic Review
Richter Transformation in Chronic Lymphocytic Leukemia
Richter transformation (RT) is defined as the occurrence of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). It is characterized by a switch in the histopathology and biology of the original CLL.
  • 1.2K
  • 24 Mar 2022
Topic Review
Therapeutic Implications of Splanchnic Vein Thrombosis
Splanchnic vein thrombosis (SVT) includes portal (portal vein thrombosis, PVT), mesenteric (mesenteric vein thrombosis, MVT) and splenic vein thrombosis, and Budd-Chiari syndrome (BCS). SVT is generally classified as secondary to an identified risk factor or primitive, unprovoked, when causative factors cannot be identified. While much rarer than common venous thromboembolism (VTE), SVT is often challenging to clinicians for both the identification of the causal disorder and for its therapeutic management. The therapeutic approach of SVT is a clinical challenge and considers the manifestations and the site of thrombosis, the risk of SVT progression, recurrence and bleeding. The decision regarding when to start, as well as the type and the duration of anticoagulant therapy is often made empirically.
  • 1.2K
  • 09 May 2023
Topic Review
Aptamers for Multiple Myeloma Precision Medicine
Multiple Myeloma (MM) is a clonal B-cell neoplasm characterized by the uncontrolled proliferation and accumulation of malignant plasma cells (PCs) in the bone marrow. Aptamers are short oligonucleotide ligands that bind their targets with great affinity and specificity, and can be easily conjugated to different cargoes for their cell-specific delivery.
  • 1.2K
  • 22 Nov 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.
  • 1.2K
  • 18 May 2021
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