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Topic Review
Inflammation in Sickle Cell Disease-Associated Pulmonary Complications
Sickle cell disease (SCD) is the most common monogenic blood disorder, affecting approximately 100,000 Americans and millions more worldwide. Cardiopulmonary complications are a major cause of morbidity and mortality in SCD, accounting for 32–70% of deaths. 
  • 589
  • 07 Mar 2023
Topic Review
The Biochemistry of Cysteines
Many pathologic conditions are associated with oxidative stress and have increased risk for clinically significant thrombotic events. These conditions include, but are not limited to, disorders of metabolism (e.g., dyslipidemia, diabetes mellitus, and obesity), chronic systemic inflammation, aging, cancer, infection, and blood disorders including hemoglobinopathy, and antiphospholipid syndrome. 
  • 587
  • 17 Jan 2024
Topic Review
Immune Checkpoint Blockade in Lymphoma
Immune checkpoint blockade (ICB) has revolutionized the prognosis of several advanced-stage solid tumors. However, its success has been far more limited in hematological malignancies and is mostly restricted to classical Hodgkin lymphoma (cHL) and primary mediastinal B cell lymphoma (PMBCL). In patients with non-Hodgkin lymphoma (NHL), response to PD-1/PD-L1 ICB monotherapy has been relatively limited, although some subtypes are more sensitive than others. Numerous predictive biomarkers have been investigated in solid malignancies, such as PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability (MSI), among others. 
  • 586
  • 21 Jul 2023
Topic Review
Pathogenesis of Sickle Cell Anaemia
Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the β-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerises and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. 
  • 578
  • 11 Sep 2023
Topic Review
Integrating AI and ML in Myelodysplastic Syndrome Diagnosis
Myelodysplastic syndrome (MDS) is composed of diverse hematological malignancies caused by dysfunctional stem cells, leading to abnormal hematopoiesis and cytopenia. Approximately 30% of MDS cases progress to acute myeloid leukemia (AML), a more aggressive disease. Early detection is crucial to intervene before MDS progresses to AML. Artificial intelligence (AI) involves computer programs that can think like humans, and machine learning (ML) is a part of AI that helps computers learn patterns and make predictions. By using these technologies, doctors can improve how they diagnose MDS, leading to better treatment and outcomes for patients.
  • 578
  • 21 Feb 2024
Topic Review
Targeted Therapies for Chronic Lymphocytic Leukemia
The management of chronic lymphocytic leukemia (CLL) is based on symptom severity and includes various types of targeted therapies, including rituximab, obinutuzumab, ibrutinib, acalabrutinib, zanubrutinib, idelalisib, and venetoclax. These therapies rely on the recognition of specific peptides presented by human leukocyte antigen (HLA)  on the surface of tumor cells by T cells, leading to an immune response. The therapeutic landscape for CLL is diverse and encompasses multiple therapeutic options, including chemotherapy, immunotherapy, radiation therapy, and stem-cell transplantation. There are several FDA-approved targeted therapies for CLL, including rituximab, ibrutinib, idelalisib, venetoclax, and acalabrutinib. Despite their high efficacy, the complex biology of CLL allows malignant cells to develop resistance mechanisms to these targeted therapies.
  • 576
  • 12 Jun 2023
Topic Review
Single-Cell Next-Generation Sequencing
Single-cell DNA sequencing is a laboratory technique that analyzes the genetic content of individual cells. In the context of genetically diverse hematological cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), the traditional approach of analyzing genetic material, which typically involves bulk samples of leukemia cells, may miss important mutations that may not be present in all cells.
  • 574
  • 12 Jul 2023
Topic Review
Invasive Mucormycosis in Patients with Hematological Malignancies
The incidence rate of invasive mucormycosis (IM) in patients with hematological malignancies (HMs) is increasing year by year, ranging from 0.07% to 4.29%, and the mortality rate is mostly higher than 50%. With the ongoing pandemic of COVID-19, COVID-19-associated mucormycosis (CAM) also became a global health threat.
  • 568
  • 30 May 2023
Topic Review
Predisposing Factors of B-Cell Non-Hodgkin’s Lymphoma
In pSS, chronic antigenic stimulation gradually drives the evolution from polyclonal B-cell expansion to oligoclonal/monoclonal B-cell predominance to malignant B-cell transformation. Thus, most pSS-related lymphomas are B-cell non-Hodgkin lymphomas (NHLs), with mucosa-associated lymphoid tissue (MALT) lymphomas predominating, followed by diffuse large B-cell lymphomas (DLBCLs) and nodal marginal zone lymphomas (NMZLs).
  • 564
  • 10 Nov 2022
Topic Review
Non-Coding RNAs in Myelodysplastic Neoplasms
Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia, and increased risk of evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs, serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis.
  • 562
  • 16 Oct 2023
Topic Review
Hematopoietic Stem Cell Transplant
Hematopoietic stem cell transplantation (HSCT) or Bone marrow transplantation is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). It is most often performed for people with diseases of the blood or bone marrow, or certain types of cancer. Bone marrow transplantation was pioneered at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Dr. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease. Since the early 1990s and the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoeitic stem cell transplantation procedures have been performed with stem cells collected from the peripheral blood. Collecting stem cells provides a bigger graft, and does not require that the donor be subjected to general anesthesia to collect the graft. Hematopoeitic stem cell transplantation remains a risky procedure and has always been reserved for patients with life threatening diseases.
  • 561
  • 11 Nov 2022
Topic Review
Infections Secondary to Targeted Therapies in Hematological Malignancies
Concurrent infections in hematological malignancies (HM) are major contributors to adverse clinical outcomes, including prolonged hospitalization and reduced life expectancy. Individuals diagnosed with HM are particularly susceptible to infectious pathogens due to immunosuppression, which can either be inherent to the hematological disorder or induced by specific therapeutic strategies. The treatment paradigm for HM has witnessed a tremendous shift, from broad-spectrum treatment approaches to more specific targeted therapies. The therapeutic landscape of HM is constantly evolving due to the advent of novel targeted therapies and the enhanced utilization of these agents for treatment purposes. By initiating unique molecular pathways, these agents hinder the proliferation of malignant cells, consequently affecting innate and adaptive immunity, which increases the risk of infectious complications.
  • 557
  • 12 Jun 2023
Topic Review
CD123 in Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients.
  • 557
  • 30 Jan 2024
Topic Review
Pediatric Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by large T-cells with strong CD30 and ALK expression. Although conventional chemotherapy is effective in most patients, approximately 30% experience a relapse or refractory disease and have a poor prognosis. Several risk factors associated with poor prognosis have been identified in pediatric ALK-positive ALCL. These include morphological patterns with the small cell variant or lymphohistiocytic variant, leukemic presentation, the presence of minimal disseminated disease, or involvement of the central nervous system. Relapsed or refractory ALK-positive ALCL is often resistant to conventional chemotherapy; therefore, salvage therapy is required. In recent years, targeted therapies such as ALK inhibitors and brentuximab vedotin (BV) have been developed. ALK inhibitors block the continuous activation of ALK kinase, a driver mutation that leads to cell proliferation in ALK-positive ALCL. Additionally, BV is an antibody–drug conjugate that targets CD30-positive cells. Both ALK inhibitors and BV have displayed dramatic effects in chemoresistant ALK-positive ALCL. Weekly vinblastine treatment and hematopoietic stem cell transplantation have also been reported to be effective therapies. 
  • 556
  • 29 Dec 2023
Topic Review
COVID-19 and Adult Acute Leukemia
The majority of publications regarding SARS-CoV-2 infections in adult patients with acute leukemia (AL) refer to hematological patients in general and are not focused on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Overall, SARS-CoV-2-associated mortality ranges from 20–52% in patients with adult AL. AML patients have a particularly high COVID-19-related mortality. Of note, most of the available data relate to the pre-vaccination era and to variants before Omicron. The impact of COVID-19 infections on AL treatment is rarely reported. Treatment delay does not appear to be associated with an increased risk of relapse, whereas therapy discontinuation was associated with worse outcomes in AML patients. Therefore, the recommendations suggest delaying systemic AL treatment in SARS-CoV-2-positive patients until SARS-CoV-2 negativity, if immediate AL treatment is not required. It is recommended to offer vaccination to all AL patients; the reported antibody responses are around 80–96%. Seronegative patients should additionally receive prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies. Patients with AL infected with SARS-CoV-2 should be treated early with antiviral therapy to prevent disease progression and enable the rapid elimination of the virus.
  • 554
  • 11 Aug 2022
Biography
Jan Evangelista Dyr
Jan was born on 24 September 1946 in Prague, Czechoslovakia. He obtained his undergraduate degree in Macromolecular Chemistry from the University of Chemistry and Technology in Prague in 1969. Then, he earned a Ph.D. in Physical Chemistry in 1978 from Charles University and a DrSc. in Chemistry in 1994 from the Academy of Sciences of the Czech Republic. In 1984 he became the Head of the Departm
  • 552
  • 31 Aug 2022
Topic Review
Autologous Stem Cell Transplantation in Multiple Myeloma
Multiple myeloma (MM) is a clonal plasma cells hematologic malignancy. The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). 
  • 550
  • 07 Mar 2022
Topic Review
Krüppel-Like Factor 1 in Erythropoiesis
Krüppel-like factor 1 (KLF1) is an erythroid-specific transcription factor that plays a crucial role in erythropoiesis. Isolated for the first time from mouse erythroleukemia cell line (MEL), it was originally named erythroid Krüppel-like factor (EKLF). When related Krüppel-like factors were subsequently identified, the nomenclature was changed to KLF1 to reflect the order of discovery. The human KLF1 gene is located on chromosome 19p13.2, whilst the mouse Klf1 gene is located on chromosome 8. KLF1 is a master erythroid gene regulator whose relevance in erythroid development and haemoglobin switching became clear as soon as the first Klf1 KO mouse models were characterised. The process of erythropoiesis occurs in different organs during mammalian embryonic development. Primitive erythropoiesis occurs in the yolk sac, in which primitive erythroid precursors (i.e., erythroid-colony-forming cells, Ery-CFCs) arise and further differentiate in the bloodstream. Definitive erythropoiesis occurs in the foetal liver until birth and subsequently in the bone marrow. Definitive erythroblasts mature in specialised niches called erythroblastic islands, which are characterised by the central macrophages of erythroid islands (CMEIs) surrounded by maturing erythroblasts, which play a fundamental role in erythropoiesis homeostasis and nuclei digestion. Both Ery-CFC and definitive erythroid progenitors (BFU-E/CFU-E), undergo a further phase of differentiation, called terminal erythropoiesis starting from large nucleated cells, proerythroblasts, that differentiate to basophil, then polychromatic and, finally, orthochromatic erythroblasts.
  • 533
  • 20 Oct 2022
Topic Review
COVID-19, HLH and Pregnant/Postpartum Women
The term ‘cytokine storm’ (CS) applies to a pathological autoimmune reaction when the interactions that lead to cytokine production are destabilised and may even lead to death. CS may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is noteworthy that many of the criteria used to diagnose haemophagocytic lymphohistiocytosis (HLH) are described as COVID-19 mortality predictors. Cytokine storms are considered to be an important cause of death in patients with the severe course of SARS-CoV-2 infection. Due to the fact that pregnant women are in an immunosuppressive state, viral pulmonary infections are more perilous for them—possible risks include miscarriage, intrauterine growth restriction or birth before the term; sometimes ventilation support is needed. HLH should be considered in pregnant and puerperal women suffering from moderately severe to severe COVID-19 and presenting with: fever unresponsive to antibiotic therapy, cytopenia, hepatitis and hyperferritinaemia.
  • 527
  • 26 Sep 2023
Topic Review
Treatment Strategies for Older Myeloma Patients
While novel therapies have improved outcomes in multiple myeloma (MM), physicians are calling for greater caution when managing this hematologic malignancy in older patients due to their fragility, which increases their vulnerability to toxic events. Additionally, this patient population may be excluded from clinical trials due to comorbidities, whereby available data are not always applicable in real-word clinical practice.
  • 525
  • 08 Jun 2023
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