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Topic Review
Geriatric Assessment-Driven Interventions in Older Adults with Cancer
Comprehensive geriatric assessment is defined as a multi-dimensional, multi-disciplinary diagnostic and therapeutic process that is conducted to determine the medical, mental, and functional problems that older people with frailty have so that a coordinated and integrated plan for treatment and follow-up can be developed. Progress has been made in the definition of the best way to detect problems, but the benefits are mostly based on prognosis stratification and on the adaptation of cancer treatment.
  • 680
  • 06 Apr 2022
Topic Review
Myeloproliferative Related Dermatosis with Indolent Clinical Outcomes
Myeloid neoplasms and acute leukemias include different entities that have been recently re-classified taking into account molecular and clinicopathological features. Two major articles were published in 2022, the ICC and the WHO classifications. The myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category comprises a heterogeneous group of hybrid neoplastic myeloid diseases characterized by the co-occurrence of clinical and pathological features of both myelodysplastic and myeloproliferative neoplasms. The most frequent entity in this category is chronic myelomonocytic leukemia (CMML) which is, after acute myeloid leukemia (AML), the main myeloid disorder prone to develop cutaneous manifestations.
  • 672
  • 04 Jan 2024
Topic Review
The Ca2+ Sensor STIM in Human Diseases
The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca2+ entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca2+ sensors in the endoplasmic reticulum (ER) and, upon Ca2+ store discharge, interact with and activate the Orai/CRACs in the plasma membrane. Dysregulation of Ca2+ signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders. 
  • 670
  • 19 Oct 2023
Topic Review
Interleukins and Thrombopoiesis
Interleukins, a diverse family of cytokines produced by various cells, play crucial roles in immune responses, immunoregulation, and a wide range of physiological and pathological processes. In the context of megakaryopoiesis, thrombopoiesis, and platelet function, interleukins have emerged as key regulators, exerting significant influence on the development, maturation, and activity of megakaryocytes (MKs) and platelets. 
  • 668
  • 24 Jan 2024
Topic Review
Models of Philadelphia-negative Chronic Myeloproliferative Neoplasms
Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions. Many of the discoveries on the pathogenesis of MPNs are due to in vivo and in vitro models that have made it possible to reproduce this type of pathology more and more faithfully.
  • 665
  • 03 Aug 2022
Topic Review
Oncolytic Viruses for Multiple Myeloma
Oncolytic virus (OV)  can infect both normal and malignant cells, but malignant cells provide a superior environment due to the presence of aberrant signalling pathways, abnormal homeostasis, and responses to stress, which are advantageous for viral replication, such as overexpressed surface attachment receptors, activated RAS or Akt, or defective IFN pathways.
  • 662
  • 13 Jan 2022
Topic Review
Wilms’ Tumor Gene
WT1 was initially identified as a tumor-suppressor gene involved in the pathogenesis of childhood renal Wilms’ tumor. The gene is located on chromosome 11 (band 11p13) and encodes for a zinc finger DNA-binding protein with four major isoforms, each of which plays a significant role in normal gene function.
  • 662
  • 22 Jun 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. 
  • 662
  • 12 Aug 2022
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.
  • 655
  • 11 Mar 2022
Topic Review
Applications of Artificial Intelligence in Thrombocytopenia
Thrombocytopenia is a medical condition where blood platelet count drops very low. This drop in platelet count can be attributed to many causes including medication, sepsis, viral infections, and autoimmunity. Clinically, the presence of thrombocytopenia might be very dangerous and is associated with poor outcomes of patients due to excessive bleeding if not addressed quickly enough. Hence, early detection and evaluation of thrombocytopenia is essential for rapid and appropriate intervention for these patients. Since artificial intelligence is able to combine and evaluate many linear and nonlinear variables simultaneously, it has shown great potential in its application in the early diagnosis, assessing the prognosis and predicting the distribution of patients with thrombocytopenia.
  • 650
  • 16 Mar 2023
Topic Review
N6-Methyladenosine (m6A) Methylation Modifications in Hematological Malignancies
Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m6A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m6A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents.
  • 647
  • 29 Jan 2022
Topic Review
Myeloid Leukemia of Down Syndrome
Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent entity, occurring with unique clinical and molecular features. The presence of a long preleukemic, myelodysplastic phase, called transient abnormal myelopoiesis (TAM), precedes the initiation of ML-DS and is defined by unusual chromosomal findings.
  • 647
  • 07 Jul 2023
Topic Review
Extracellular Matrix Metabolism
Chronic inflammation in myeloproliferative neoplasms (MPNs) is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). The connective tissue responds uniformly to injuries of any kind by distinctive sequential changes in the ECM expression, including oedema formation, angiogenesis and finally, fibrosis, with the deposition of type III collagen in the early phase, mainly as fine fibers, and type I collagen as coarse fibers in the later phase of the lesion). This injury–repair process is qualitatively similar in all organs and is accompanied by the release of various matrix components into the circulation during the synthesis and breakdown of connective tissue constituents at the site of injury.
  • 638
  • 11 Dec 2023
Topic Review
Chimeric Antigen Receptor T Cell Therapy in AML
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. Adoptive cell therapy using chimeric antigen receptors (CAR) has shown promise in B cell malignancies and is being investigated in AML.
  • 638
  • 19 Jan 2024
Topic Review
MRD in Autografts Might Predict Clinical Outcome
Proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies (triple class drugs), and autologous stem cell transplantation (ASCT) are promising myeloma treatments that have resulted in minimal residual disease (MRD) negativity and improvement in the bone marrow microenvironment.
  • 635
  • 06 May 2023
Topic Review
Clonal Evolution Detected by Next-Generation Sequencing
Unlike with chemotherapy, which imparts a relatively short duration of selective pressure on acute myeloid leukemia clonal architecture, the immunological effect related to allogeneic hematopoietic stem cell transplant is prolonged over time and must be overcome for relapse to occur. This means that not all molecular abnormalities detected after transplant always imply inevitable relapse. Therefore, transplant represents a critical setting where a measurable residual disease-based strategy, performed during post-transplant follow-up by highly sensitive methods such as next-generation sequencing, could optimize and improve treatment outcome.
  • 630
  • 18 May 2023
Topic Review
Human Hematopoietic Stem/Progenitor Cells in T1DM Treatment
Type 1 diabetes mellitus (T1DM) is a highly prevalent autoimmune disease causing the destruction of pancreatic islet β-cells. The resulting insulin production deficiency leads to a lifelong need for insulin re-placement therapy, systemic complications, and reduced life quality and expectancy. Cell therapy has been extensively attempted to restore insulin independence (IID), and autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has appeared to give the most promising results.
  • 628
  • 19 Apr 2023
Topic Review
Techniques for Monitoring of MRD in AML
After diagnosis of acute myeloid leukemia (AML), patients undergo chemotherapy, achieving complete remission (CR) in the majority of cases. However, some residual leukemic cells (up to 1010 to 1012 cells) can remain undetectable, causing a high percentage of patients to relapse. This condition is conventionally referred to as minimal residual disease, although more recently this nomenclature has been replaced by measurable residual disease (MRD). The term “measurable” was proposed to indicate some contexts where Leukemic Stem Cell (LSC) levels are detectable by modern technologies that have a high sensitivity. MRD monitoring in AML is performed routinely in clinical practice since it is a strong indicator of relapse. Besides, MRD can also have implications in the planning and personalization of treatment, when assessed in conjunction with other well-established clinical, cytogenetic, and molecular data. Furthermore, it has been shown that when MRD detection is successfully performed at an early stage, it results in improved prognosis, disease management, and patient outcome. Some of the currently used techniques for MRD assessment in AML are multiparametric flow cytometry (MFC) and molecular-based techniques, such as reverse transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS), further described below.
  • 626
  • 27 Mar 2023
Topic Review
Venetoclax in the Treatment of Younger AML Patients
The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML). This innovative approach has led to higher rates of overall response, measurable residual disease (MRD)-negative remissions, and overall survival compared with AZA monotherapy. As a result, this combination has emerged as the gold-standard treatment for elderly or unfit patients with AML who are not eligible for intensive therapy. In younger, fit patients with AML, intensive induction and consolidation chemotherapy is commonly used as a first-line approach; however, relapse continues to be the main reason for treatment failure in approximately 30–40% of patients. Efforts to improve MRD-negative response rates and to facilitate the transition to allogeneic hematopoietic stem cell transplantation, particularly in high-risk AML, have inspired trials exploring the combination of intensive chemotherapy with targeted agents. VEN, a first-in-class anti-BCL2 agent, combined with intensive chemotherapy regimens has shown deep MRD-negative remissions, producing prolonged event-free survival and enhancing the transition to allogeneic transplant in first-complete-remission patients. These benefits support the incremental advantages of adding VEN to intensive chemotherapy approaches across ELN risk subcategories, and provides a robust benchmark to design future trials.
  • 626
  • 09 Jan 2024
Topic Review
Prognostic Factors for Cardiotoxicity among Children with Cancer
Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity.
  • 623
  • 13 Jun 2023
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