scholarly journals Acute Myeloid Leukemia: Focus on novel Therapeutic Strategies

2012 ◽  
Vol 6 ◽  
pp. CMO.S7244 ◽  
Author(s):  
Tara L. Lin ◽  
M. Yair Levy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Risk Groups ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Recent Advances ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid ◽  
Novel Therapeutic

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies.

Epitranscriptomic modifications in acute myeloid leukemia: m6A and 2′-O-methylation as targets for novel therapeutic strategies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Cornelius Pauli ◽  
Michael Kienhöfer ◽  
Stefanie Göllner ◽  
Carsten Müller-Tidow
Keyword(s):  
Acute Myeloid Leukemia ◽  
Ribosomal Rna ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Rna Modifications ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid

Abstract Modifications of RNA commonly occur in all species. Multiple enzymes are involved as writers, erasers and readers of these modifications. Many RNA modifications or the respective enzymes are associated with human disease and especially cancer. Currently, the mechanisms how RNA modifications impact on a large number of intracellular processes are emerging and knowledge about the pathogenetic role of RNA modifications increases. In Acute Myeloid Leukemia (AML), the N 6-methyladenosine (m6A) modification has emerged as an important modulator of leukemogenesis. The writer proteins METTL3 and METTL14 are both involved in AML pathogenesis and might be suitable therapeutic targets. Recently, close links between 2′-O-methylation (2′-O-me) of ribosomal RNA and leukemogenesis were discovered. The AML1-ETO oncofusion protein which specifically occurs in a subset of AML was found to depend on induction of snoRNAs and 2′-O-me for leukemogenesis. Also, NPM1, an important tumor suppressor in AML, was associated with altered snoRNAs and 2′-O-me. These findings point toward novel pathogenetic mechanisms and potential therapeutic interventions. The current knowledge and the implications are the topic of this review.

Tribbles in acute leukemia

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4265-4270 ◽  
Author(s):  
Kai Ling Liang ◽  
Loveena Rishi ◽  
Karen Keeshan
Keyword(s):  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Therapeutic Strategies ◽  
Acute Leukemias ◽  
Hematopoietic Malignancies ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid ◽  
Novel Therapeutic

Abstract There is growing research interest in the mammalian Tribbles (Trib) family of serine/threonine pseudokinases and their oncogenic association with acute leukemias. This review is to understand the role of Trib genes in hematopoietic malignancies and their potential as targets for novel therapeutic strategies in acute myeloid leukemia and acute lymphoblastic leukemia. We discuss the role of Tribs as central signaling mediators in different subtypes of acute leukemia and propose that inhibition of dysregulated Trib signaling may be therapeutically beneficial.

Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients

2007 ◽  
Vol 25 (14) ◽  
pp. 1908-1915 ◽  
Author(s):  
Elihu Estey
Keyword(s):  
Acute Myeloid Leukemia ◽  
Natural History ◽  
Lower Risk ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Specific Treatment ◽  
Risk Groups ◽  
The Elderly ◽  
History Of ◽  
Acute Myeloid

The median age of patients with acute myeloid leukemia (AML) is 65 to 70 years. The majority of older patients with AML probably do not receive specific treatment, and those who receive standard regimens have a median survival time of less than 1 year. This suggests that, in general, older patients should receive investigational therapy; however, factors other than age influence survival after administration of standard treatment and need to be accounted for when making treatment recommendations. In some cases where investigational therapy is unavailable, palliative care may be the best option. Like AML, myelodysplastic syndrome (MDS) is a disease of the elderly. It is divided into higher and lower risk groups. The natural history of high-risk MDS (eg, > 10% marrow blasts) bears more resemblance to that of AML than to that of an indolent disorder; accordingly, similar therapeutic considerations apply. The more benign natural history of lower risk MDS leads to consideration of reduction in transfusion needs and improvement in quality of life as primary goals of therapy. Lenalidomide, azacitidine, and decitabine, each recently approved by the US Food and Drug Administration, are useful in achieving these objectives.

Treatment of acute myeloid leukemia – a single center experience (2007–2013)

2014 ◽  
Vol 155 (17) ◽  
pp. 653-658
Author(s):  
Anna Selmeczi ◽  
Miklós Udvardy ◽  
Árpád Illés ◽  
Béla Telek ◽  
Attila Kiss ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
The Elderly ◽  
Blood Cell Count ◽  
Apparent Effect ◽  
Single Center Experience ◽  
Prognostic Group ◽  
Minimal Residual ◽  
Acute Myeloid

Introduction: Mortality of acute myeloid leukemia is still 60–70% in young (<60 years) adults and 90% in elderly (≥60 years) patients. Aim: The aim of the authors was to analyse the outcome of treatment in their patients with acute myeloid leukemia. Method: From 2007 to 2013, 173 patients with acute myeloid leukemia were treated. Patients were classified according to the European LeukemiaNet prognostic guideline. Association between mortality and the type of acute myeloid leukemia (secundary or primary), dose of daunoblastin at induction of treatment, and the rate of minimal residual disease were investigated. Results: The 5-year survival probability was 25% in young adults and 2% in the elderly. The survival was significantly influenced by these prognostic factors. The 5-year survival rate was 50% in the young, favorable prognostic group. The 90 mg/m2daunoblastin dose was found to be beneficial. Addition of bortezomib to the standard induction protocol had an additional beneficial effect. Conclusions: The speed and depth of the response to induction therapy, and the initial white blood cell count had an apparent effect on survival. Orv. Hetil., 2014, 155(17), 653–658.

scholarly journals Targeting Metabolic Reprogramming in Acute Myeloid Leukemia

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 967 ◽  
Author(s):  
Isabel Castro ◽  
Belém Sampaio-Marques ◽  
Paula Ludovico
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Therapeutic Window ◽  
Tumor Proliferation ◽  
Preclinical Models ◽  
Promote Tumor Growth ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid

The cancer metabolic reprogramming allows the maintenance of tumor proliferation, expansion and survival by altering key bioenergetics, biosynthetic and redox functions to meet the higher demands of tumor cells. In addition, several metabolites are also needed to perform signaling functions that further promote tumor growth and progression. These metabolic alterations have been exploited in different cancers, including acute myeloid leukemia, as novel therapeutic strategies both in preclinical models and clinical trials. Here, we review the complexity of acute myeloid leukemia (AML) metabolism and discuss how therapies targeting different aspects of cellular metabolism have demonstrated efficacy and how they provide a therapeutic window that should be explored to target the metabolic requirements of AML cells.

Recent advances in antigen-loaded dendritic cell-based strategies for treatment of minimal residual disease in acute myeloid leukemia

Immunotherapy ◽  
2010 ◽  
Vol 2 (1) ◽  
pp. 69-83 ◽  
Author(s):  
Willemijn van den Ancker ◽  
Marvin M van Luijn ◽  
Theresia M Westers ◽  
Hetty J Bontkes ◽  
Jurjen M Ruben ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Dendritic Cell ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Recent Advances ◽  
Minimal Residual ◽  
Acute Myeloid
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