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Topic review
Updated time: 27 Aug 2021
Submitted by: Adam Zayac
Definition: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy affecting about 0.5% of people in their lifetime. Over the last few decades, a growing understanding of AML has revealed it to be a heterogenous disease with a widely variable prognosis. This is largely driven by disease biology, the ability to tolerate highly toxic multi-agent chemotherapy and, in most cases, undergo allogeneic stem cell transplantation to be cured of disease.
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Topic review
Updated time: 25 May 2021
Submitted by: Fengjuan Fan
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.
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Topic review
Updated time: 12 Aug 2021
Submitted by: Katie Dunphy
Definition: The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease.
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Topic review
Updated time: 29 Jul 2021
Submitted by: Elisabetta Abruzzese
Definition: Acute myeloid leukemia (AML), the most frequent acute leukemia in adults, has been historically treated with infusional cytarabine (ara-c) + daunorubicin (3 + 7) for at least 40 years. The first “target therapy” to be introduced was the monoclonal anti-CD33 gemtuzumab ozogamicin (GO) in 2004.
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Topic review
Updated time: 12 May 2021
Submitted by: Michael T. McCurdy
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.
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Topic review
Updated time: 15 Oct 2021
Submitted by: Michele Gottardi
Definition: Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by genetic and clinical heterogeneity and high mortality. Gemtuzumab Ozogamicin (GO) is a drug approved for the treatment of acute myeloid leukemia (AML). It targets leukemic cells that express the CD33 molecule on their surface and brings the toxic agent calicheamicin inside the cell to kill it. AML patients can benefit of the addition of GO to chemotherapy during induction regimens, pre- and post-transplantation.
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Topic review
Updated time: 07 Sep 2021
Submitted by: Ioanna STERGIOU
Definition: Hematopoiesis is a stepwise process through which hematopoietic stem cells (HSCs) differentiate to progenitor cells that demonstrate a restricted potential and eventually further differentiate to form all mature blood and immune cells.
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Topic review
Updated time: 10 Sep 2021
Submitted by: Joost Koedijk
Definition: Immunotherapy may be an attractive treatment option to increase survival, and to reduce treatment-related side effects, for children with acute myeloid leukemia (AML). While immunotherapies have shown successes in many cancer types, the development and subsequent clinical implementation have proven difficult in pediatric AML. To expedite the development of immunotherapy, it will be crucial to understand which pediatric AML patients are likely to respond to immunotherapies. Emerging research in solid malignancies has shown that the number and phenotype of immune cells in the tumor microenvironment is predictive of response to several types of immunotherapies. Such a predictive model may also be applicable for AML and, thus, knowledge on the immune cells infiltrating the bone marrow environment is needed. Here, we discuss the current state of knowledge on these infiltrating immune cells in pediatric AML, as well as ongoing immunotherapy trials, and provide suggestions concerning the way forward.
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Topic review
Updated time: 25 Apr 2021
Submitted by: Paolo Gresele
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.
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Topic review
Updated time: 18 May 2021
Submitted by: Inge Lodewijckx
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.
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