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Topic Review
ABCG2 in Acute Myeloid Leukemia
ABCG2 is an efflux transporter responsible for inducing multidrug resistance (MDR) in leukemic cells; through its ability to extrude many antineoplastic drugs, it leads to AML resistance and/or relapse. Moreover, ABCG2 may be co-expressed with other MDR-related proteins and is finely regulated by epigenetic mechanisms. 
  • 789
  • 25 May 2023
Topic Review
Macrophage–Erythrocyte Interactions in Sickle Cell Disease Erythropoiesis
Sickle cell disease (SCD) is an inherited blood disorder caused by a β-globin gene point mutation that results in the production of sickle hemoglobin that polymerizes upon deoxygenation, causing the sickling of red blood cells (RBCs). Macrophages participate in extravascular hemolysis by removing damaged RBCs, hence preventing the release of free hemoglobin and heme, and triggering inflammation. Upon erythrophagocytosis, macrophages metabolize RBC-derived hemoglobin, activating mechanisms responsible for recycling iron, which is then used for the generation of new RBCs to try to compensate for anemia. In the bone marrow, macrophages can create specialized niches, known as erythroblastic islands (EBIs), which regulate erythropoiesis. Anemia and inflammation present in SCD may trigger mechanisms of stress erythropoiesis, intensifying RBC generation by expanding the number of EBIs in the bone marrow and creating new ones in extramedullary sites. 
  • 788
  • 06 Apr 2023
Topic Review
MDSCs in haematological malignancies
Myeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors (ICIs). Currently, multiple studies at the preclinical and clinical levels seek to use this cell population for the treatment of different haematological neoplasms, together with ICIs. 
  • 787
  • 26 May 2021
Topic Review
Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation
Endothelial dysfunction (ED) is frequently encountered in transplant medicine. After hematopoietic stem cell transplantation (HSCT), ED participates in the pathogenesis of various complications such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy (TA-TMA), idiopathic pneumonia syndrome (IPS), capillary leak syndrome (CLS), and engraftment syndrome (ES).
  • 786
  • 29 Mar 2022
Topic Review
Treatment of Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a heterogenous disease with a broad spectrum of cytogenetic and molecular aberrations contributing to the definition of distinct AML subgroups. Treatment options for patients suffering from AML are continuously expanding and targeted therapies are available for distinct molecularly defined subgroups. Nevertheless, AML treatment remains challenging; in particular, patients with high-risk AML not eligible for intensive treatment or allogeneic hematopoietic stem cell transplantation (alloHSCT) are characterized by an unfavorable outcome.
  • 785
  • 02 Dec 2021
Topic Review
PI3K/Akt/mTOR Signaling Pathway in Blood Malignancies
Blood malignancies remain a therapeutic challenge despite the development of numerous treatment strategies. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway plays a central role in regulating many cellular functions, including cell cycle, proliferation, quiescence, and longevity. Therefore, dysregulation of this pathway is a characteristic feature of carcinogenesis.
  • 783
  • 04 Dec 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.
  • 782
  • 24 Sep 2021
Topic Review
Targeted Drug Delivery for Blood Cancers
Blood cancers are a type of liquid tumor which means cancer is present in the body fluid. Multiple myeloma, leukemia, and lymphoma are the three common types of blood cancers. Chemotherapy is the major therapy of blood cancers by systemic administration of anticancer agents into the blood. However, a high incidence of relapse often happens, due to the low efficiency of the anticancer agents that accumulate in the tumor site, and therefore lead to a low survival rate of patients. This indicates an urgent need for a targeted drug delivery system to improve the safety and efficacy of therapeutics for blood cancers.
  • 780
  • 15 Apr 2022
Topic Review
CAR T Cell Therapy for Chronic Lymphocytic Leukemia
Chimeric antigen receptor T (CAR T) cell therapy is promising for relapse/refractory chronic lymphocytic leukemia (CLL) patients. Complete and durable remission of CLL is possible in patients treated with CAR T cells but further investigations are necessary to understand and possibly predict how patient specific factors influence the outcome of this treatment.
  • 772
  • 20 Jun 2022
Topic Review
Diagnosis, Pathogenesis, and Treatment of T-Cell Prolymphocytic Leukemia
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms.
  • 770
  • 02 Aug 2023
Topic Review
Follicular Lymphoma and Primary Splenic Lymphoma
Follicular lymphoma (FL) is a mature B-cell non-Hodgkin lymphoma derived from germinal center B-lymphocytes (centrocytes and centroblasts) that generally has at least a partially follicular/nodular histologic pattern.
  • 764
  • 25 Nov 2021
Topic Review
The Immune Landscape in Myelodysplastic Syndromes
The Revised International Prognostic Scoring System (IPSS-R) is used to estimate the MDS patients’ risk of AML progression and overall survival (OS). In clinical settings, patients with an IPSS-R score of 3.5 or less represent a lower-risk MDS group (median survival; 5.9 years), whereas an IPSS-R score > 3.5 falls into the higher-risk MDS group (median survival; 1.5 years). The lower-risk disease is associated with an inflammatory microenvironment and increased cell death, in contrast to higher-risk disease, which is delineated by immunosuppression and clonal expansion. 
  • 763
  • 20 Jun 2022
Topic Review
Gene-Edited-αβ T Cells
Multiple Myeloma (MM), characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA (anti-B cell maturation antigen) chimeric antigen receptor (CAR)-T cells are one of the Food and Drug Administration (FDA)-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for more patients. In general, anti-BCMA CAR gene-edited αβ T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR-γδ T cells and CAR-invariant Natural Killer T (iNKT) cells are still in pre-clinical studies. Inactivation of the endogenous TCR (T cell’s receptor) by genome engineering methods is one of the most promising strategies for generating αβ T cells for allogeneic use. 
  • 762
  • 07 Feb 2023
Topic Review
Extramedullary Relapse of FLT3-ITD Acute Myeloid Leukemia
FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase family member. Mutations in FLT3, as well known, represent the most common genomic alteration in acute myeloid leukemia (AML), identified in approximately one-third of newly diagnosed adult patients. In recent years, this has represented an important therapeutic target. Drugs such as midostaurin, gilteritinib, and sorafenib, either alone in association with conventional chemotherapy, play a pivotal role in AML therapy with the mutated FLT3 gene. A current challenge lies in treating forms of AML with extramedullary localization. 
  • 756
  • 06 Jun 2022
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.
  • 753
  • 23 Mar 2022
Topic Review
Bone Marrow Transplantation in Thalassemia
Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allogeneic stem cell transplantation (allo-SCT). However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. 
  • 753
  • 06 May 2023
Topic Review
The Role of MRD Monitoring
Measurable (“minimal”) residual disease (MRD) is defined as the post-therapy persistence of leukemic cells at levels below the morphologic detection limit. Mounting evidence indicates that the presence of MRD is a strong, independent prognostic marker of increased risk of relapse and of shorter survival in patients with acute leukemia compared with patients with a negative MRD test. MRD assessment primarily involves the determination of leukemia-associated immunophenotypic patterns (LAIP) using multiparameter flow cytometry (MCF) and the polymerase chain reaction (PCR)-based evaluation of expression levels of leukemia-related genes (specific reciprocal gene rearrangements and other mutation types). In addition, next-generation sequencing and digital PCR may further enrich current MRD-detection methods. Adding the MRD evaluation to other post-treatment assessments could be of help in guiding the post-remission treatment strategies by identifying patients at high risk of relapse who might benefit from pre-emptive therapy. Several studies have clearly shown that treatment is more effective if at molecular relapse with a low disease burden than at overt relapse.
  • 752
  • 24 Feb 2022
Topic Review
Hemostatic Abnormalities in Gaucher Disease
Gaucher disease (GD) is an autosomal recessive lysosomal storage disease that is caused by deficiency of the enzyme β-glucocerebrosidase (β-GCase), which is required for the degradation of glycosphingolipids. Deficiency of β-GCase is responsible for the accumulation of glucosylceramide and its deacylated product glucosylsphingosine into lysosomes of reticuloendothelial cells. These lipid-laden cells are known as Gaucher cells. Gaucher cells are large and characterized by eccentric nuclei, condensed chromatin and cytoplasm with heterogeneous “crumpled tissue paper”. The bone marrow, spleen and liver are particularly infiltrated by these cells in GD, leading to the main clinical signs of the disease at diagnosis.
  • 748
  • 02 Dec 2022
Topic Review
Diagnosis of Primary Vitreoretinal Lymphoma
Intraocular lymphomas (IOLs) include vitreoretinal lymphomas (VRLs) and primary uveal or choroidal lymphomas. VRLs are further subdivided into primary VRLs and secondary VRLs, the latter deriving from systemic lymphomas. Primary uveal or choroidal lymphomas are usually low-grade neoplasms and are frequently extranodal marginal zone lymphomas with very good outcomes, unlike primary vitreoretinal lymphomas (PVRLs) which are high-grade diseases with poor outcomes. Secondary IOLs derive from ocular involvement by systemic lymphomas through haematogenous spread. Systemic lymphomas mainly disseminate to the uvea, due to its rich blood flow. PVRL represents a diagnostic challenge for both clinicians and pathologists, and it is critical, for the patient’s life, to shorten the time between the onset of symptoms often mistaken for chronic uveitis and correct diagnosis. Different laboratory methods are in use to diagnose PVRL. The main employed techniques are described, highlighting the principal diagnostic issues with the different laboratory methods.
  • 746
  • 18 Oct 2022
Topic Review
Novel Monoclonal Antibodies in B-Cell Non-Hodgkin Lymphoma Treatment
NMABs represent a heterogeneous group of agents, including naked antibodies, immunotoxins, and T-cell-engaging molecules. Several NMABs have either gained regulatory approval or are on the verge of introduction into clinical practice, addressing multiple therapeutic indications and treatment regimens. Their anticipated impact is expected to be broad, initially in the context of relapsed/refractory (R/R) disease and subsequently extending to early treatment lines.
  • 746
  • 15 Dec 2023
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