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Topic Review
TP53 Alterations in MDS and AML
TP53 mutations are less frequent in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) than in solid tumors, except in secondary and therapy-related MDS/AMLs, and in cases with complex monosomal karyotype. As in solid tumors, missense mutations predominate, with the same hotspot mutated codons (particularly codons 175, 248, 273). As TP53-mutated MDS/AMLs are generally associated with complex chromosomal abnormalities, it is not always clear when TP53 mutations occur in the pathophysiological process.
  • 213
  • 28 Apr 2023
Topic Review
Toll-like Receptors in Hematology
Toll-like receptors (TLR) belong to the pattern recognition receptors (PRR). TLRs are primarily expressed in hematopoietic cells. TLRs also direct the formation of blood cellular components and make a contribution to the pathogenesis of certain hematopoietic malignancies. 
  • 238
  • 22 May 2023
Topic Review
Thrombosis and Immune Checkpoint Inhibitors
Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies.
  • 426
  • 24 Sep 2021
Topic Review
Therapy of Relapsed/Refractory Mantle Cell Lymphoma after BTKis
Mantle cell lymphoma (MCL) is a rare mature B-cell non-Hodgkin lymphoma (B-NHL) with historically poor outcomes. Virtually all patients will eventually experience refractory or relapsed (R/R) disease, with a virulent course of resistance and serial relapses, making treatment challenging. The available therapies for R/R MCL are not curative with conventional therapy, their goal being to palliate and prolong survival. A variety of agents approved for R/R MCL, including Bruton’s tyrosine kinase inhibitors (BTKi), changed the treatment landscape of R/R MCL. In the pre-BTKi era, the median progression-free survival (PFS) in R/R disease was 4–9 months. With the introduction of ibrutinib, the median PFS improved to 13–14.6 months. Despite these impressive results, the duration of response is limited, and resistance to BTKi inevitably develops in a subset of patients. Outcomes after progression on BTKi are extremely poor, with a median overall survival (OS) of 6 to 10 months. Certain therapies, such as chimeric antigen receptor (CAR) T cells, have shown promising results after BTKi failure. The preferred combination and sequencing of therapies beyond BTKi remain unestablished.
  • 344
  • 23 Mar 2022
Topic Review
Therapies for Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) arises directly from pDC over-expansion. BPDCN is a rare hemopathy classified among acute myeloid leukemia (AML) since 2008 by the World Health Organization (WHO). As a specific entity since 2016, it represents <1% of AML. No benchmark treatment exists for BPDCN. Since this rare malignancy is chemo-sensitive, chemotherapy followed by hematopoietic stem cell transplantation remains an effective treatment. However, relapses frequently occur with the development of resistance. New options arising with the development of therapies targeting signaling pathways and epigenetic dysregulation have shown promising results. 
  • 261
  • 12 Aug 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.
  • 462
  • 28 Jan 2022
Topic Review
Therapeutic Strategies Targeting the Exosomes in Multiple Myeloma
Multiple myeloma (MM) is a malignancy of plasma cells in the bone marrow and is characterized by the clonal proliferation of B-cells producing defective monoclonal immunoglobulins. Despite the developments in treatment, drug resistance remains one of the major challenges in the therapy of MM. The crosstalk between MM cells and other components within the bone marrow microenvironment (BME) is the major determinant of disease phenotypes. Exosomes have emerged as the critical drivers of this crosstalk by allowing the delivery of informational cargo comprising multiple components from miniature peptides to nucleic acids. Such material transfers have now been shown to perpetuate drug-resistance development and disease progression in MM. MicroRNAs(miRNAs) specifically play a crucial role in this communication considering their small size that allows them to be readily packed within the exosomes and widespread potency that impacts the developmental trajectory of the disease inside the tumor microenvironment (TME).
  • 340
  • 11 Apr 2023
Topic Review
Therapeutic Plasmapheresis with Albumin Replacement in Alzheimer’s Disease
Reducing the burden of beta-amyloid accumulation and toxic autoimmunity-related proteins, one of the recognized pathophysiological markers of chronic and common neurological disorders such as Alzheimer’s disease (AD) and multiple sclerosis (MS), may be a valid alternative therapy to reduce their accumulation in the brain and thus reduce the progression of these disorders.
  • 336
  • 11 Mar 2022
Topic Review
Therapeutic Landscape of Peripheral T-Cell Lymphomas
T-cell lymphomas are a relatively rare group of malignancies with a diverse range of pathologic features and clinical behaviors. Recent molecular studies have revealed a wide array of different mechanisms that drive the development of these malignancies and may be associated with resistance to therapies. 
  • 389
  • 29 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.
  • 249
  • 09 May 2023
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