Acute myeloid leukemia therapy and the chosen people

Estey, Elihu H.; Gale, Robert Peter

doi:10.1038/leu.2016.306

Cited by 13 publications

(6 citation statements)

References 26 publications

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“…Hematopoietic stem cell (HSC), cluster of differentiation (CD), hematopoietic progenitor cell (HPC), common myeloid progenitor (CMP), common lymphoid progenitor (CLP), interleukin (IL), granulocyte macrophage (GM) colony-stimulating-factor (CSF), stem cell factor (SCF), thrombopoietin (TPO), erythropoietin (EPO), granulocyte myeloid progenitor (GMP), runt-related transcription factor 1 (RUNX1), transcription factor stem cell leukemia (SCL), ccaat enhancer binding proteins (C/EBP), friend of GATA protein 1 (FOG-1). 60's to a particularly bleak 10% [12]. In ALL, recent advances for example in the use of tyrosine kinase inhibitors and CAR-T cell therapy, have started to suggest improvements to overall survival [10].…”

Section: Human Hematopoiesis Schematic Diagram Showing Classical Model Of Hematopoietic Lineage Commitment With Phenotypical Cell Surfacementioning

confidence: 99%

Reactive Oxygen Species and Metabolic Re-Wiring in Acute Leukemias

Robinson¹,

Darley²,

Tonks³

2021

Acute Leukemias

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Reactive oxygen species (ROS) is the collective term for several oxygen containing free radicals, such as hydrogen peroxide. ROS is important in innate immunity, protein folding in the endoplasmic reticulum and as a cell signalling molecule involved in cellular proliferation, survival, differentiation, and gene expression. ROS has been implicated in both hematopoietic stem cell quiescence and hematopoietic differentiation. Consequently, ROS is of considerable interest as a therapeutic target, with both pro-oxidant and anti-oxidant cellular modulation being explored. Recently, it has been established that increased ROS production in acute myeloid leukemia (AML) leads to increased glycolysis and metabolic reprogramming. It is often stated as a key tenet of the Warburg effect, that transformed cells, including AML, show increased aerobic glycolysis accompanied by increased cellular glucose uptake and lactate secretion. This review will summarize ROS state of the art in acute leukemia and how these reactive molecules re-wire metabolism in cancer cells. The review will focus on what are ROS? What are the sources of ROS in hematopoietic cells and their function and how this relates to the Warburg effect and regulation of metabolic pathways in acute leukemias.

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Section: Human Hematopoiesis Schematic Diagram Showing Classical Model Of Hematopoietic Lineage Commitment With Phenotypical Cell Surfacementioning

confidence: 99%

Reactive Oxygen Species and Metabolic Re-Wiring in Acute Leukemias

Robinson¹,

Darley²,

Tonks³

2021

Acute Leukemias

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“…Recently, a variety of novel therapeutic agents have been approved by both the US Food and Drug Administration and the European Medicines Agency for frontline treatment of patients with AML; long-term benefits remain uncertain, however, and study design as well as eligibility criteria may be flawed. [66][67][68] ML provides the means to improve patient selection, recruitment, and monitoring in clinical trials by assessing eligibility criteria, scanning electronic health records for suitable patients, or predicting the likelihood of failure or success in a trial. 69 ML models have been established in drug discovery and development, and DNNs especially show tremendous potential in identifying biomarkers and druggable targets and in the assessment of potential therapeutic molecules.…”

Section: Treatment and Prognosismentioning

confidence: 99%

Application of machine learning in the management of acute myeloid leukemia: current practice and future prospects

Bornhäuser

Wendt²,

Middeke

2020

Blood Advances

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Machine learning (ML) is rapidly emerging in several fields of cancer research. ML algorithms can deal with vast amounts of medical data and provide a better understanding of malignant disease. Its ability to process information from different diagnostic modalities and functions to predict prognosis and suggest therapeutic strategies indicates that ML is a promising tool for the future management of hematologic malignancies; acute myeloid leukemia (AML) is a model disease of various recent studies. An integration of these ML techniques into various applications in AML management can assure fast and accurate diagnosis as well as precise risk stratification and optimal therapy. Nevertheless, these techniques come with various pitfalls and need a strict regulatory framework to ensure safe use of ML. This comprehensive review highlights and discusses recent advances in ML techniques in the management of AML as a model disease of hematologic neoplasms, enabling researchers and clinicians alike to critically evaluate this upcoming, potentially practice-changing technology.

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“…However, these trials have implicit selection bias. 3,4 As is well known to this audience, far too many patients are not enrolled in clinical trials, for a myriad of reasons. Selection bias not only limits generalizability of the results, but also means that the results likely overestimate success, such as it is.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic therapy in acute myeloid leukemia: not quite dead yet

Michaelis

2018

Hematology

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Given the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients. Indeed, the future likely lies in combinations of therapies that act with a spectrum of mechanisms. Using a case-based format, this review will outline current treatment expectations for patients according to karyotypic risk and familiarize readers with the basis for common induction choices. Relapsed/refractory disease may be especially amenable to interventions with novel agents or clinical trials; however, there are still some patients who most benefit from intensive chemotherapy. This review will outline risk systems that help the practitioner identify those with the best chances for response and survival. Finally, clinical tools, including geriatric assessments and comorbidity calculators, may help clinicians recognize patients for whom disease risk and comorbidity tip the balance against classical chemotherapy, a frequent challenge for those who treat this devastating disease.

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Acute myeloid leukemia therapy and the chosen people

Cited by 13 publications

References 26 publications

Reactive Oxygen Species and Metabolic Re-Wiring in Acute Leukemias

Reactive Oxygen Species and Metabolic Re-Wiring in Acute Leukemias

Application of machine learning in the management of acute myeloid leukemia: current practice and future prospects

Cytotoxic therapy in acute myeloid leukemia: not quite dead yet

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