scholarly journals Canonical Wnt; a safeguard and threat for Erythropoiesis

2021 ◽  
Author(s):  
Rosa Anna Krimpenfort ◽  
Micha Nethe
Keyword(s):  
Myeloid Leukemia ◽  
Treatment Options ◽  
Comprehensive Overview ◽  
Hematopoietic Stem ◽  
Stress Erythropoiesis ◽  
Chronic Activation ◽  
Canonical Wnt ◽  
Insight Into ◽  
Hsc Transplantation ◽  
Acute Myeloid

Myeloid dysplastic syndrome (MDS) reflects a preleukemic BM disorder with limited treatment options and poor disease survival1. As only a minority of MDS patients is eligible to curative hematopoietic stem cell (HSC) transplantation, there is an urgent need to develop alternative treatment options. Chronic activation of Wnt/β-catenin has been implicated to underlie MDS formation and recently assigned to drive MDS transformation to acute myeloid leukemia (AML). Wnt/β-catenin signaling therefore may harbor a pharmaceutical target to treat MDS and/or prevent leukemia formation. However, targeting the Wnt/β-catenin pathway will also affect healthy hematopoiesis in MDS patients.The control of Wnt/β-catenin on healthy hematopoiesis is poorly understood. Whereas Wnt/β-catenin is dispensable for steady-state erythropoiesis, its activity is essential for stress erythropoiesis in response to BM injury and anemia. Manipulation of Wnt/β-catenin signaling in MDS may therefore deregulate stress erythropoiesis and even increase anemia severity. Here we provide a comprehensive overview of the most recent and established insights in the field to acquire more insight into the control of Wnt/β-catenin signaling on healthy and inefficient erythropoiesis as seen in MDS.

scholarly journals Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia

2019 ◽  
Vol 8 (5) ◽  
pp. 579 ◽  
Author(s):  
Heleen H. Van Acker ◽  
Maarten Versteven ◽  
Felix S. Lichtenegger ◽  
Gils Roex ◽  
Diana Campillo-Davo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Immune Cells ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Survival Rates ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem ◽  
Clonal Proliferation ◽  
Elderly Aml ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a type of blood cancer characterized by the uncontrolled clonal proliferation of myeloid hematopoietic progenitor cells in the bone marrow. The outcome of AML is poor, with five-year overall survival rates of less than 10% for the predominant group of patients older than 65 years. One of the main reasons for this poor outcome is that the majority of AML patients will relapse, even after they have attained complete remission by chemotherapy. Chemotherapy, supplemented with allogeneic hematopoietic stem cell transplantation in patients at high risk of relapse, is still the cornerstone of current AML treatment. Both therapies are, however, associated with significant morbidity and mortality. These observations illustrate the need for more effective and less toxic treatment options, especially in elderly AML and have fostered the development of novel immune-based strategies to treat AML. One of these strategies involves the use of a special type of immune cells, the dendritic cells (DCs). As central orchestrators of the immune system, DCs are key to the induction of anti-leukemia immunity. In this review, we provide an update of the clinical experience that has been obtained so far with this form of immunotherapy in patients with AML.

scholarly journals Progressive Dispersion of Azole Resistance in Aspergillus fumigatus: Fatal Invasive Aspergillosis in a Patient with Acute Myeloid Leukemia Infected with an A. fumigatus Strain with a cyp51A TR46 Y121F M172I T289A Allele

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Susann Rößler ◽  
Oliver Bader ◽  
Friedrich Stölzel ◽  
Ulrich Sommer ◽  
Birgit Spiess ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
Azole Resistance ◽  
Hematopoietic Stem ◽  
Content Type ◽  
Acute Myeloid

ABSTRACT Patients with hematologic malignancies as well as allogeneic hematopoietic stem cell transplantation (HSCT) patients are at high risk for invasive aspergillosis. Here, we report a culture- and autopsy-proven fatal invasive aspergillosis in an allogeneic HSTC patient which he developed despite posaconazole prophylaxis. The agent was determined to be an azole-resistant Aspergillus fumigatus strain bearing the cyp51A mutation combination TR46 Y121F M172I T289A. At increasing frequency, the azole resistance of A. fumigatus is being reported globally, limiting treatment options and complicating regimens.

scholarly journals Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5722
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Andreas Hochhaus ◽  
Sebastian Scholl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Epigenetic Therapy ◽  
Comprehensive Overview ◽  
Secondary Resistance ◽  
Acute Myeloid

Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients.

scholarly journals How I treat refractory and early relapsed acute myeloid leukemia

Blood ◽  
2015 ◽  
Vol 126 (3) ◽  
pp. 319-327 ◽  
Author(s):  
Felicitas Thol ◽  
Richard F. Schlenk ◽  
Michael Heuser ◽  
Arnold Ganser
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Salvage Chemotherapy ◽  
Hematopoietic Stem ◽  
Bridge To Transplant ◽  
Unfit Patients ◽  
Clinical Conditions ◽  
Acute Myeloid

AbstractBetween 10% and 40% of newly diagnosed patients with acute myeloid leukemia (AML) do not achieve complete remission with intensive induction therapy and are therefore categorized as primary refractory or resistant. Few of these patients can be cured with conventional salvage therapy. They need to be evaluated regarding eligibility for allogeneic hematopoietic stem cell transplantation (HSCT) as this is currently the treatment with the highest probability of cure. To reduce the leukemia burden prior to transplantation, salvage chemotherapy regimens need to be employed. Whenever possible, refractory/relapsed patients should be enrolled in clinical trials as we do not have highly effective and standardized treatments for this situation. Novel therapies include tyrosine kinase inhibitors, small-molecule inhibitors (eg, for Polo-like kinase 1 and aminopeptidase), inhibitors of mutated isocitrate dehydrogenase (IDH) 1 and IDH2, antibody-based therapies, and cell-based therapies. Although the majority of these therapies are still under evaluation, they are likely to enter clinical practice rapidly as a bridge to transplant and/or in older, unfit patients who are not candidates for allogeneic HSCT. In this review, we describe our approach to refractory/early relapsed AML, and we discuss treatment options for patients with regard to different clinical conditions and molecular profiles.

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