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Topic Review
Potential Therapeutic Targets in Lymphoma
Lymphoma is a heterogeneous group of diseases that often require their metabolism programs to fulfill the demand of cell proliferation. Features of metabolism in lymphoma cells include high glucose uptake, deregulated expression of enzymes related to glycolysis, dual capacity for glycolytic and oxidative metabolism, elevated glutamine metabolism, and fatty acid synthesis. These aberrant metabolic changes lead to tumorigenesis, disease progression, and resistance to lymphoma chemotherapy. Metabolic reprogramming, including glucose, nucleic acid, fatty acid, and amino acid metabolism, is a dynamic process caused not only by genetic and epigenetic changes, but also by changes in the microenvironment affected by viral infections. Notably, some critical metabolic enzymes and metabolites may play vital roles in lymphomagenesis and progression. 
  • 1.0K
  • 07 Apr 2023
Topic Review
NK Cells for Adoptive Immunotherapy
NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challanges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly overcome by pioneering trials that focused on harnessing NK cell functions. Recent technology advancements in gene delivery, gene editing and chimeric antigen receptor (CARs) have made it possible to generate genetically modified NK cells that enhance the anti-tumor efficacy and represent suitable 'off-the-shelf' products with fewer side effects. The recent advanced in NK cell biology along with current approaches for potentiating NK cell proliferation and activity was highlighted, redirecting NK cells using CARs and optimizing the procedure to manufacture clinical-grade NK and CAR NK cells for adoptive immunotherapy.
  • 1.0K
  • 27 Sep 2021
Topic Review
Metabolic Reprogramming in Sickle Cell Diseases
Sickle cell disease (SCD) is a genetic disorder that affects millions of individuals worldwide. Chronic anemia, hemolysis, and vasculopathy are associated with SCD, and their role has been well characterized. These symptoms stem from hemoglobin (Hb) polymerization, which is the primary event in the molecular pathogenesis of SCD and contributes to erythrocyte or red blood cell (RBC) sickling, stiffness, and vaso-occlusion. The disease is caused by a mutation at the sixth position of the β-globin gene, coding for sickle Hb (HbS) instead of normal adult Hb (HbA), which under hypoxic conditions polymerizes into rigid fibers to distort the shapes of the RBCs. Only a few therapies are available, with the universal effectiveness of recently approved therapies still being monitored. 
  • 1.0K
  • 18 Jul 2022
Topic Review
Evaluation of Treatment Response in Multiple Myeloma
Bone disease is among the defining characteristics of symptomatic Multiple Myeloma (MM). Imaging techniques such as fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) can identify plasma cell proliferation and quantify disease activity. This function renders these imaging tools as suitable not only for diagnosis, but also for the assessment of bone disease after treatment of MM patients. 
  • 1.0K
  • 16 Jan 2023
Topic Review
Myelodysplastic Syndromes with Isolated del(5q)
Myelodysplastic syndromes (MDS) are a group of clonal hematological neoplasms characterized by ineffective hematopoiesis in one or more bone marrow cell lineages. Myelodysplastic syndromes with isolated del(5q) constitute the only MDS subtype defined by a cytogenetic alteration. 
  • 1.0K
  • 16 Nov 2022
Topic Review
Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms
The myelodysplastic syndromes/myeloproliferative overlap neoplasms (MDS/MPN) comprise a heterogeneous group of myeloid neoplastic diseases with clinical and pathologic overlapping features of both myelodysplastic and myeloproliferative neoplasms. The 2016 World Health Organization (WHO) classification included five entities: chronic myelomonocytic leukemia (CMML), atypical CML BCR-ABL1− (aCML), juvenile myelomonocytic leukemia (JMML), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and MDS/MPN unclassifiable (MDS/MPN-U). In 2022, there emerged two competing classifications for myeloid neoplasms: the International Consensus Classification (ICC) and the fifth edition of the WHO classification. Both classifications now expand on these categories; in particular, MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) has been split into two entities in the ICC 2022 based on the presence/absence of the SF3B1 mutation. Moreover, both the WHO 2022 classification and the ICC move JMML to be grouped with pediatric and/or germline mutation-associated disorders.
  • 1.0K
  • 21 Jun 2023
Topic Review
Biofluids in Haematological Malignancies
The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease.
  • 1.0K
  • 12 Aug 2021
Topic Review
Primary Hemostasis Disorders in Women of Reproductive Age
Heavy menstrual bleeding (HMB) is a common clinical condition affecting adolescent and adult women and compromising their quality of life. Primary hemostasis disorders, affecting platelet plug formation, can be the underlying cause of HMB. They comprise a heterogeneous group of diseases with Von Willebrand disease (VWD) being the most commonly diagnosed; other disorders in this group that have been linked to HMB include (a) Glanzmann thrombasthenia, (b) Bernard–Soulier syndrome, (c) Hermansky–Pudlak syndrome, (d) immune thrombocytopenia (ITP), and (e) Ehlers–Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Diagnosing these diseases can be challenging, as the basic laboratory investigations can be within the normal range.
  • 1.0K
  • 19 Oct 2023
Topic Review
The Genomics of Hairy Cell Leukaemia
Hairy cell leukaemia is a rare chronic lymphoid malignancy with distinctive clinical and laboratory features which include an enlarged spleen, low blood counts, and infiltration of the spleen and bone marrow, with lymphocytes that have a villous or hairy cytoplasmic border. Historically it has been responsive to a range of treatment modalities including splenectomy, alpha interferon, and more recently chemotherapy, but none are curative. The Genomics of hairy cell leukaemia involves the chromosome abnormalities, genomic mutations, DNA methylation patterns, and immunoglobulin gene usage in this disease.
  • 986
  • 10 Mar 2022
Topic Review
Biomarkers of Thromboembolic Risk in Atrial Fibrillation
An ideal biomarker should be simple and practical, have a high sensitivity and be inexpensive. Some clinical markers (e.g., non-paroxysmal type of AF, carotid plaque) and some circulating biomarkers (e.g., cardiac troponin, N-terminal pro-B-type natriuretic protein [BT-proBNP], and D-dimer) are promising for use in IS prediction in patients with NVAF because it is both practical and simple to determine them.
  • 983
  • 28 Feb 2022
Topic Review
NOTCH Signaling in Mantle Cell Lymphoma
The NOTCH signaling pathway is highly conserved, and its dysregulation has been implicated in the pathogenesis of many B cell malignancies including MCL, chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and multiple myeloma (MM). The NOTCH genes play a critical role in the early and late phases of normal B cell differentiation. In MCL, mutations in the PEST domain stabilize NOTCH proteins, rendering them resistant to degradation, which subsequently results in the upregulation of genes involved in angiogenesis, cell cycle progression, and cell migration and adhesion.
  • 958
  • 20 Jun 2023
Topic Review
Immunotherapy for Hodgkin's lymphoma
The introduction of immunotherapy into the treatment options for Hodgkin’s lymphoma has improved survival in patients with recurrence of their cancer. These agents help the body’s immune system respond and clear cancer cells. 
  • 955
  • 11 Jul 2022
Topic Review
Oxidative Stress in Red Blood Cell Diseases
Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases.
  • 954
  • 29 Aug 2023
Topic Review
Genomics of Plasma Cell Leukemia
Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell dyscrasia characterized by the presence of clonal circulating plasma cells in peripheral blood. PCL accounts for approximately 2–4% of all multiple myeloma (MM) cases. PCL can be classified in primary PCL (pPCL) when it appears de novo and in secondary PCL (sPCL) when it arises from a pre-existing relapsed/refractory MM. The development of new high-throughput technologies, such as microarrays and new generation sequencing (NGS), has contributed to a better understanding of the peculiar biological and clinical features of this disease. Relevant information is now available on cytogenetic alterations, genetic variants, transcriptome, methylation patterns, and non-coding RNA profiles. Additionally, attempts have been made to integrate genomic alterations with gene expression data. 
  • 950
  • 11 May 2022
Topic Review
Ferroptosis in NAFLD
Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease with steatosis as the main pathological feature, including simple fatty liver degeneration, non-alcoholic steatohepatitis (NASH). It may develop into cirrhosis and liver cancer. NAFLD is the most common chronic liver disease in the world today, and its incidence in the Euro-American region has reached more than 20%.
  • 949
  • 20 Dec 2021
Topic Review
Next-Generation Covalent BTKi
Ibrutinib revolutionized the chronic lymphocytic leukemia (CLL) treatment approach and prognosis demonstrating its efficacy and safety even at extended follow-up. During the last few years, several next-generation inhibitors have been developed to overcome the occurrence of toxicity or resistance in patients on continuous treatment. In a head-to-head comparison of two phase III trials, both acalabrutinib and zanubrutinib demonstrated a lower incidence of adverse events in respect to ibrutinib. Nevertheless, resistance mutations remain a concern with continuous therapy and were demonstrated with both first- and next-generation covalent inhibitors. Reversible inhibitors showed efficacy independently of previous treatment and the presence of bruton tyrosine kinase (BTK) mutations. Other strategies are currently under development in CLL, especially for high-risk patients, and include BTK inhibitor combinations with BCl2 inhibitors with or without anti-CD20 monoclonal antibodies. New mechanisms for BTK inhibition are under investigations in patients progressing with both covalent and non-covalent BTK and BCl2 inhibitors. 
  • 949
  • 30 Mar 2023
Topic Review
How Azanucleosides Affect Myeloid Cell Fate
The azanucleosides decitabine and azacytidine are used widely in the treatment of myeloid neoplasia and increasingly in the context of combination therapies. Although they are both classed as hypomethylating agents, their modes of actions differ. Decitabine reduces DNA methylation generally, while azacytidine reduces RNA methylation at a specific subset of sites. The hypomethylating agents have overlapping, but distinct effects on neoplastic cells that are likely to have consequences for their clincal use, particularly in the context of combination therapies.
  • 943
  • 01 Sep 2022
Topic Review
Disseminated Intravascular Coagulation
Disseminated intravascular coagulation (DIC) is a serious condition involving widespread, persistent activation of coagulation in the presence of underlying disease, resulting in diffuse microthrombi in small blood vessels. Although significant activation of coagulation is always observed in DIC, the degree of fibrinolytic activation depends on the underlying disease or condition. Depending on the degree of fibrinolytic activation, DIC can be classified into three disease types.
  • 941
  • 21 Mar 2022
Topic Review
Targeting the B-Cell Receptor in Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is characterized by a high degree of clinical heterogeneity that is influenced by the disease’s molecular complexity. The genes most frequently affected in CLL cluster into specific biological pathways, including B-cell receptor (BCR) signaling, apoptosis, NF-κB, and NOTCH1 signaling. BCR signaling and the apoptosis pathway have been exploited to design targeted medicines for CLL therapy.
  • 939
  • 24 Feb 2022
Topic Review
Therapeutic Target for β-Thalassemia Patients
Iron homeostasis is regulated by hepcidin, a hepatic hormone that controls dietary iron absorption and plasma iron concentration. Hepcidin binds to the only known iron export protein, ferroportin (FPN), which regulates its expression. The major factors that implicate hepcidin regulation include iron stores, hypoxia, inflammation, and erythropoiesis. When erythropoietic activity is suppressed, hepcidin expression is hampered, leading to deficiency, thus causing an iron overload in iron-loading anemia, such as β-thalassemia. Iron overload is the principal cause of mortality and morbidity in β-thalassemia patients with or without blood transfusion dependence. In the case of thalassemia major, the primary cause of iron overload is blood transfusion. In contrast, iron overload is attributed to hepcidin deficiency and hyperabsorption of dietary iron in non-transfusion thalassemia. Beta-thalassemia patients showed marked hepcidin suppression, anemia, iron overload, and ineffective erythropoiesis (IE). Recent molecular research has prompted the discovery of new diagnostic markers and therapeutic targets for several diseases, including β-thalassemia.
  • 924
  • 28 Jan 2022
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