Volume 2, Issue 2, p36-72
Articles published in this issue are Open Access and licensed under Creative Commons Attribution License (CC BY NC) where the readers can reuse, download, distribute the article in whole or part by mentioning proper credits to the authors.
Chemotherapy Promotes Release of Exosomes Which Upregulate Cholesterol Synthesis and Chemoresistance in AML Blasts
Extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication as well as a major mechanism of functional reprogramming of cells in disease. All cells produce EVs, which freely circulate and are found in all body fluids. EVs are heterogenous, consisting of subsets of vesicles with different sizes, distinct origins, and various functions (Figure 1). They mediate a broad variety of biological events ranging from cellular activation, inflammation, blood coagulation, angiogenesis, cellular transport, and others. Among these vesicles, a subset of small EVs (30-150 nm in diameter) originating from multivesicular bodies (MVBs) in parent cells and referred to as small extracellular vesicles (sEVs) carry proteomic, genomic and functional signatures that resemble those of parent cells and are, therefore, taken as surrogates of parent cells. In cancer, tumor-derived exosomes (TEX) reflect characteristics of tumor cells and are considered candidates for “liquid tumor biopsy”. Emerging evidence shows that TEX are a major sEV subset in plasma of patients with cancer, including hematologic malignancies.J Clin Haematol, 2021, Volume 2, Issue 2, p36-39 | DOI: 10.33696/haematology.2.026
Platelet transfusion is associated with the risk of sepsis from bacterial contamination due to the need to store units at room temperature in oxygen-permeable bags. This risk associated with platelet transfusion is highest among all transfusable blood components. Measures applied in the past several decades have significantly reduced the occurrence of patient morbidity and mortality but have not eliminated it totally. Sampling of processed platelets for bacterial culture after 24 hours post-collection lowered the rate of infection but still allowed contaminated transfusions to occur due to low levels of bacteria being missed during sampling. Bacteria entering log phase growth after 24 hours may not be detected.J Clin Haematol, 2021, Volume 2, Issue 2, p40-47 | DOI: 10.33696/haematology.2.027
Flavopiridol (Alvocidib), a Cyclin-dependent Kinases (CDKs) Inhibitor, Found Synergy Effects with Niclosamide in Cutaneous T-cell Lymphoma
Flavopiridol (FVP; alvocidib), an FDA-approved orphan drug, has been studied in clinical trials under both single treatment and combination scenarios; several singleagent Phase I and Phase II clinical trials against leukemia, lymphomas, and solid tumors are active. To date, there have been more than 50 clinical trials involving FVP in the United States. Unfortunately, almost half of patients on FVP clinical trials showed serious adverse effects, implicating appropriate dosages need to be found and an alternative way to circumvent the toxicity of FVP with synergistic agents.J Clin Haematol, 2021, Volume 2, Issue 2, p48-61 | DOI: 10.33696/haematology.2.028
Physiology, Coagulation Cascade: Inherited Disorders, and the Molecular Phenomenon of Alterations in Hemostasis
The physiology of coagulation routes and paths is a cascade of several molecular phenomena and biological events which was classified into two categories based on their phenomena i.e., intrinsic and extrinsic, originated separately, consisting of various factors and features such as fibrinogen, prothrombin, plasma thromboplastin, Hageman factor, Christmas factor, and Stuart-Prower factor, participate in its physiologyJ Clin Haematol, 2021, Volume 2, Issue 2, p62-64 | DOI: 10.33696/haematology.2.029
Prediction of Severity and Mortality in Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Utility of Clinical-biological Scores
Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening thrombotic microangiopathy (TMA). It has an average annual prevalence of approximately 10 cases/million people and an annual incidence between 1.5 and 6.0 cases per million according to studies conducted in France, the United States, the United Kingdom, and Spain. The first episode of aTTP occurs mostly during adulthood (~90% of all aTTP cases), but some child and adolescent forms are also detected (~10% of cases).J Clin Haematol, 2021, Volume 2, Issue 2, p65-72 | DOI: 10.33696/haematology.2.030
Karyotypic Profile of Chronic Myeloid Leukemia in Patients Diagnosed at Tertiary Level in Afghanistan
Balanced translocation resulting in fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2 is the pathognomonic molecular driver of CML. The resulting BCRABL 1 fusion gene is both the diagnostic as well as therapeutic target of CML. The first agent with tyrosine kinase inhibitor activity that was licenced in 2000 for treatment of CML patients, was Imatinib, gradually followed by multiple agents with higher efficacy.
Lipoprotein(a) [Lp(a)] is a genetically determined lowdensity lipoprotein (LDL) particle that is comprised of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB) moieties. It is well-established that elevated Lp(a) is an independent risk factor for cardiovascular disease (CVD).
However, the entire coagulation cascade is dysfunctional, in progressed chronic diabetes and cancer patients.
Molecular Biology for BCR-ABL1 Quantification for Chronic Myeloid Leukemia Monitorization and Evaluation
Chronic Myeloid Leukemia (CML) is a clonal disorder originated by a pluripotent hematopoietic stem cell, which presents the translocation t(9;22) (q34;q11) in 90% of the cases.
Dexamethasone: The First Drug to be Shown to Decrease Mortality in Critically Ill Patients with COVID-19
The precise role of corticosteroids for treatment of coronavirus disease 2019 (COVID-19) is unclear due to lack of randomized trials.
Platelets are small anuclear cells shed from the megakaryocyte, at a rate of ~1011/day , maintaining a blood concentration of 100-450 x 109/L in healthy adults. As the second most abundant circulating cells, they are becoming increasingly recognized for their versatility and cross-talks in cancer, development, immunology among others.
The Novel Antiplatelet Agent Revacept in Cardiovascular Medicine: The Promise of Efficacy Without Bleeding
Revacept, a dimeric fusion protein of the extracellular domain of GPVI and the human Fc-fragment, inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. Finally, the possible utility of this pharmacological approach in the prevention of tumor metastasis is discussed.
Leukemia is the most common childhood malignancy and is the most common cause of cancer death before the age of 20. Pediatric leukemia can be subdivided into acute versus chronic and lymphoid versus myeloid leukemia.
Leukemia is a tumor of the primary blood-forming cells. leukemia is not only a cancer of the white blood cells but also it originates in other blood cell types. Types of leukemia are categorized based on the rate of growth to acute (fastgrowing) or chronic (slower growing), and whether it arises in myeloid cells or lymphoid cells. Different types of leukemia have a different line of treatment and prognosis.
Lack of Prognostic Significance of Pretreatment Total Metabolic Tumor Volume on Event-free Survival at 24 Months in Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. The majority of patients benefit from chemo-immunotherapy; however, 30 to 40% relapse after first-line treatment, and 10% are refractory to first-line treatment. This variability in outcome has led to the identification of prognostic factors to stratify patients based on their risk of relapse. The five-factor international prognostic index (IPI) was formulated for such risk stratification more than 20 years ago, based on clinical information obtained from patients with aggressive lymphomas treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like chemotherapy. The addition of rituximab to CHOP chemotherapy led to improved outcomes, diminishing the discriminatory capacity of IPI amongst risk groups. Efforts to enhance the prognostic model by adding or defining new factors have only led to minor improvements without the ability to identify patients at risk of an inferior outcome.
Tumor-derived small extracellular vesicles or exosomes which carry the checkpoint PD-L1 are directly involved in immune evasion and uncontrolled tumor growth. We have recently reported that PD-L1 is also enriched on Wharton’s Jelly Mesenchymal Stromal Cell (WJMSC)-associated exosomes.
Toward Integrated Genomic Diagnosis in Routine Diagnostic Pathology by the World Health Organization Classification of Acute Myeloid Leukemia
Significant milestones and seminal discoveries during 1674-1966, by individuals who have made crucial contributions toward progress in the diagnosis of hematologic neoplasms as we understand today are depicted chronologically. It is notable that the path to progress in the understanding of disease and neoplasms initially took centuries for significant discoveries (17th-18th centuries), and subsequently, many decades (19th-20th centuries) for a breakthrough or a change from the prevailing norm.
Epidemiologic, Clinical, and Biological Characteristics of Adult T-cell Leukemia/Lymphoma in Martinique (1983- 2013)
Adult T-cell leukemia/lymphoma (ATL) was first described in the Southwest islands of Japan in 1977 . Then, the HTLV-1 (human T-lymphotropic virustype 1) was isolated in the United States in 1981 in two patients, one with mycosis fungoïdes and the other with Sezary syndrome [2,3], which have been consequently renamed.
AD is a neurodegenerative disease characterized by progressive cognitive impairment, behavioral changes, memory loss and executive dysfunction, all of which present serious threats to the health of older people.
A 56-year-old Caucasian man was referred to an academic medical center for consideration of allogeneic hematopoietic stem cell transplantation (HSCT). One year earlier, he had seen his primary care physician for increased fatigue and decreased exercise tolerance, and a complete blood cell count showed a total white blood cell count of 2500/μL, hemoglobin of 7.2g/dL, and a platelet count of 110,000/μL. The white blood cell differential showed an absolute neutrophil count of 900/μL. The patient was referred to a hematologist who performed a bone marrow biopsy that showed a myelodysplastic syndrome with del(5q).
Excessive bleeding or hemorrhage in traumatic injuries is the leading preventable cause of death in the combat and civilian trauma centers. Nearly 50% of military deaths, 90% of military battlefield casualties, and 33-56% mortalities in civilian’s surgical bleeding are associated with severe bleeding and can be prevented. Hence, significant and rapid hemostasis or bleeding control require innovative strategies with easy to use, stable, and inexpensive processing. Furthermore, the developed hemostatic material should ensure biocompatibility and biodegradability with non-immunogenic properties. To date, a wide variety of hemostatic powders, dressings, and bandages have been investigated as useful materials in reducing hemorrhage.
Chronic lymphoid leukemia (CLL) is a malignant hematological disease characterized by the accumulation of mature lymphocytes with a defect in the induction of apoptosis that massively accumulate in peripheral blood (PB), bone marrow (BM) and lymphoid tissues.
Second Generation Platelet Concentrates - L-PRF (Fibrin Rich in Platelets and Leukocytes) and Its Derivatives (A-PRF, I-PRF)-: Morphological Characteristics to be Used in Modern Regenerative Surgery. Experimental Research
Platelet preparations (PDPs) have gained success, mainly due to their high concentrations of biologically active molecules, such as growth factors and cytokines, which play an important role in tissue repair and reconstruction. Recent knowledge shows that platelets can play a new role in tissue reproduction and vascular restoration, as well as being the protagonists of inflammatory processes and immune system responses. They release bio-active proteins and other active ingredients that can affect a number of phenomena that promote cell consumption, growth and transformation (growth factors).
Unmasking the Master of Disguise: Defining Advancements in Diagnosis of Intravascular Large B-cell Lymphoma
Intravascular B cell lymphoma (IVBCL) is notoriously difficult to diagnose as the clinical manifestations are protean, and the patterns seen with routine labs and imaging are non-specific. Furthermore, the disease follows an aggressive course and is often fatal within a matter of weeks to months from symptom onset, unless recognized and treated appropriately. This has historically meant that diagnosis was made at autopsy for many patients. Over the past few decades, however, scientific and clinical literature have slowly accumulated to better characterize and raise clinical awareness of this disease. In this paper, we will review the characteristics that make this diagnosis challenging, and then discuss new and emerging diagnostic avenues.
Acute lymphoblastic leukemia (ALL) is the deterioration of the maturation period of lymphoblasts, and the uncontrolled excessive reproduction of the abnormal cells. In addition to gene rearrangements, chromosome number abormalities (Down syndrome, etc.), and genetic locations, being male, Caucasian ethnicity, having a sibling diagnosed with leukemia, exposure to radiation, having received chemotherapy or radiotherapy, and exposure to some toxins and chemical substances such as benzene may be counted as the ALL risk factors.
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