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Updated time: 25 May 2021
Definition: Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.
Updated time: 12 May 2021
Definition: Sepsis is a clinical syndrome resulting from a dysregulated inflammatory response to infection. Sepsis management demands early diagnosis and timely treatment that includes source control, antimicrobial therapy, and resuscitation.
Updated time: 25 Apr 2021
Definition: Inherited thrombocytopenias (IT) are a group of hereditary disorders characterized by a reduced platelet count sometimes associated with abnormal platelet function, which can lead to bleeding but also to syndromic manifestations and predispositions to other disorders.
Updated time: 18 May 2021
Definition: The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphocyte development and homeostasis. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function of the pathway contributes to malignant transformation. It has become increasingly clear that in lymphoid malignancies, especially in T-cell leukemia, many components of the IL-7 signaling pathway carry genetic alterations leading to increased signaling. Moreover, the majority of leukemic cells express the wild type IL-7 receptor and remain dependent on IL-7 signaling for survival, cell cycle progression and proliferation. In this review, we discuss the role of deregulated IL-7-induced JAK-STAT signaling in lymphoid malignancies of T- and B-cell origin.
Updated time: 26 May 2021
Definition: 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.
Updated time: 12 Jul 2021
Definition: Relapse is still a major problem in AML because it occurs in about 60–80% of patients, even those who have previously achieved complete remission (CR), defined by the presence of ≤5% bone marrow (BM) leukemic cells. Thus, since CR is unable to predict the relapse risk, significantly more sensitive techniques aimed at identifying AML cells in BM or peripheral blood, a parameter termed measurable residual disease (MRD), have been developed. Among them, RT-qPCR, which analyses appropriate molecular markers, and multiparameter flow cytometry (MFC), which analyses aberrantly expressed antigens, have been identified as the methods of choice for MRD detection.
Entry Collection : Stem Cells and Cancer
Updated time: 05 May 2021
Definition: Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, one or more peripheral cytopenias, single or multilineage dysplasia in the bone marrow (BM), and an increased risk of progressing to acute myeloid leukemia (AML), occurring eventually in approximately 30% of the cases, more rapidly in higher risk patients.
Updated time: 13 Jul 2021
Definition: Beta-thalassemia (β-thalassemia) is an autosomal recessive inherited disease characterized by decreased production of the β-globin chains of hemoglobin (Hb) A. The normal structure of HbA is two α- and two β-globin chains. Individuals with β-thalassemia are either homozygous or double heterozygotes for mutations in the β-globin gene.
Updated time: 21 Jun 2021
Definition: Hematologic malignancies are a heterogeneous group of diseases of diverse incidence, prognosis, and etiology that cause 1.3 million cases and more than 700,000 deaths every year worldwide. These malignancies show a stable trend in the last decades, but an increased incidence is observed for myeloma in women.
Updated time: 27 May 2021
Definition: Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic neoplasms characterized by ineffective hematopoiesis and myelodysplasia with a variable spectrum of clinical–biological features that can be used to build a prognostic estimation.