The Role of 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. This review presents a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS

Rifampicin-Induced Thrombocytopenia: A Case Report and Short Review of the Literature

Thrombocytopenia may be associated with a variety of conditions and risks depending on its severity, ranging from mild epistaxis to life-threating bleeding. Many drugs or herbal remedies can cause thrombocytopenia by either inhibiting platelet production and/or enhancing their destruction from the peripheral blood mediated via an immunological mechanism implicating drug-dependent antibodies. The latter entity is called drug-induced immune thrombocytopenia: a life-threatening, under-recognised condition, which is often a diagnostic challenge. Rifampicin is a widely used, well-tolerated, and effective bactericidal drug. Adverse events, except for gastrointestinal effects, headache, skin rash, and pruritus, are uncommon. The authors herein report on a patient with isolated thrombocytopenia with a recent medical history of brucellosis on rifampicin and doxycycline. Thrombocytopenia was proved to be rifampicin-induced. Also presented is a short review of the literature on this rare subject, which should be of great importance to clinicians

Hyponatremia in Patients with Hematologic Diseases

Hyponatremia is the most common electrolyte disorder in clinical practice and is associated with increased morbidity and mortality. It is frequently encountered in hematologic patients with either benign or malignant diseases. Several underlying mechanisms, such as hypovolemia, infections, toxins, renal, endocrine, cardiac, and liver disorders, as well as the use of certain drugs appear to be involved in the development or the persistence of hyponatremia. This review describes the pathophysiology of hyponatremia and discusses thoroughly the contributing factors and mechanisms that may be encountered specifically in patients with hematologic disorders. The involvement of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion and renal salt wasting syndrome (RSWS) in the development of hyponatremia in such patients, as well as their differential diagnosis and management, are also presented. Furthermore, the distinction between true hyponatremia and pseudohyponatremia is explained. Finally, a practical algorithm for the evaluation of hyponatremia in hematologic patients, as well as the principles of hyponatremia management, are included in this review

Luspatercept: A New Tool for the Treatment of Anemia Related to β-Thalassemia, Myelodysplastic Syndromes and Primary Myelofibrosis

Anemia is a common feature of both benign and malignant hematologic diseases. Beta-thalassemia (β-thalassemia) syndromes are a group of hereditary disorders characterized by ineffective erythropoiesis, due to a genetic deficiency in the synthesis of the beta chains of hemoglobin, often accompanied by severe anemia and the need for red blood cell (RBC) transfusions. Myelodysplastic syndromes (MDS) are characterized by cytopenia(s) and ineffective hematopoiesis, despite a hypercellular bone marrow. Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm characterized by reactive fibrosis of the bone marrow, accompanied by extramedullary hematopoiesis. Luspatercept, previously known as ACE-536, is a fusion protein that combines a modified activin receptor IIB (ActRIIB), a member of the transforming growth factor-β (TGF-β) superfamily, with the Fc domain of human immunoglobulin G (IgG1). It has shown efficacy in the treatment of anemia due to beta β-thalassemia, MDS and PMF and recently gained approval by the Federal Drug Agency (FDA) and the European Medicines Agency (EMA) for transfusion-dependent (TD) patients with β-thalassemia and very low to intermediate-risk patients with MDS with ringed sideroblasts who have failed to respond to, or are ineligible for, an erythropoiesis-stimulating agent. In this review, we describe the key pathways involved in normal hematopoiesis and the possible mechanism of action of luspatercept, present its development and data from the most recent clinical trials in β-thalassemia, MDS and PMF, and discuss its potential use in the treatment of these hematological disorders

Expression Patterns of GATA3 in Classical Hodgkin Lymphoma: A Clinico-Pathological Study

GATA3 is a transcription factor involved in T-cell maturation and has been previously shown to be aberrantly overexpressed in malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). However, the immunophenotypes of the cell types expressing GATA3 have not been precisely characterized so far in cHL tissues. In this single-center retrospective cohort study we analyzed the expression patterns of GATA3 alone and in combination with B, T, NK or macrophage-associated markers in 73 cases with newly diagnosed cHL and investigated for a possible correlation with clinical and laboratory parameters. Immunohistochemistry (single and double) was performed using GATA3 alone and in combination with CD20, CD3, CD56, CD68, CD30 or CD15. Clinical and laboratory parameters were collected and correlated with the expression of GATA 3. GATA3 nuclear expression was found in HRS cells in 39/73 (54%) cases of cHL. The Nodular Sclerosis (NS) subtype showed the highest positivity rate (35/56, 63%), followed by mixed cellularity (MC; 4/14, 29%) and lymphocyte rich (LR; 0/3). Double immunostainings showed that GATA3 was expressed by CD30+ or CD15+ HRS cells and a few CD3+ T-cells, whereas GATA3 expression was not detected in CD20, CD56 or CD68+ cells. GATA3-negative cHL was significantly associated with unfavorable prognostic factors such as older age at diagnosis and increased levels of serum β2-microglobulin. The heterogenous expression patterns of GATA3 in HRS cells that were observed in a substantial proportion of cHL, mainly in the NS subtype, further support the biological heterogeneity of cHL

CD56 expression in multiple myeloma: Correlation with poor prognostic markers but no effect on outcome

CD56 or neural cell adhesion molecule (NCAM) is a membrane glycoprotein expressed on neural cells, muscle tissues and myeloma cells. Expression of CD56 has been studied in patients with multiple myeloma (MM) with controversial results. The scope of this study was to examine the expression of CD56 in MM patients at diagnosis and investigate its association with clinicopathologic parameters. We retrospectively collected and analyzed data from 109 patients with MM diagnosed over the last decade (January 2010 to June 2020). Expression of CD56 was assessed by immunohistochemistry in bone marrow biopsies and investigated its association with a variety of clinicopathological parameters. For the statistical analysis chi(2) test and Mann-Whitney U tests were used to compare categorical and continuous variables in CD56+ and CD56- patients, respectively. Statistical analysis was performed using SPSS 21.0 for Windows (SPSS, Chicago, IL). Based on the expression of CD56 the patient population was divided to CD56+ patients and CD56- patients; Sixty-eight patients were CD56 + and 41 patients were CD56-. Absence of CD56 expression was associated with unfavorable prognostic parameters such as elevated lactate dehydrogenase (LDH) and beta 2-microglobulin levels, advanced stage according to the International Staging System (ISS) and clonal bone marrow plasma cell infiltration >= 60%, but no effect on outcome, while the expression of CD56 was associated with well differentiated neoplastic plasma cells. Our study confirmed that lack of CD56 expression is a possible marker of poor prognosis in patients with MM. The detection of CD56 expression by either immunohistochemistry or flow cytometry is simple and cheap, and it could be incorporated in future prognostic or predictive scores. Prospective studies are needed in order to evaluate the role of expression of CD56 as a predictive biomarker in the era of novel regimens