scholarly journals Noncoding RNAs in Acute Myeloid Leukemia: From Key Regulators to Clinical Players

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Alessandro Fatica
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tumor Suppressor Genes ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Aberrant Expression ◽  
Genetic Abnormalities ◽  
Non Coding Rnas ◽  
Recent Demonstration ◽  
Acute Myeloid

Recent analyses have shown that human cells transcribe almost their entire genomes, implying the existence of a huge mass of ncRNAs. At the present, microRNAs are the most investigated regulative non-coding RNAs. Several studies have demonstrated that microRNAs play a crucial role in hematopoietic differentiation and hematological malignancies, including acute myeloid leukemia (AML). Aberrant expression of microRNAs has been associated with specific genetic abnormalities and clinical outcome of patients with AML. In addition, since microRNAs can function as either oncogenes or tumor suppressor genes, the potential of using these molecules as therapeutic targets opens up new opportunities in the future of AML therapy. The recent demonstration that other regulatory ncRNAs, in addition to microRNAs, are involved in hematopoietic cell differentiation and diseases, suggests that they may also have a biological relevance in AML. This paper will describe the role of ncRNAs in AML and discuss the expectations for the use of ncRNAs in diagnosis, prognosis, and therapy of AML.

scholarly journals Therapeutic Resistance in Acute Myeloid Leukemia: The Role of Non-Coding RNAs

2016 ◽  
Vol 17 (12) ◽  
pp. 2080 ◽  
Author(s):  
Armin Zebisch ◽  
Stefan Hatzl ◽  
Martin Pichler ◽  
Albert Wölfler ◽  
Heinz Sill
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Therapeutic Resistance ◽  
Non Coding Rnas ◽  
Acute Myeloid

scholarly journals Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia

Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3563-3572 ◽  
Author(s):  
Omar Abdel-Wahab ◽  
Ross L. Levine
Keyword(s):  
Acute Myeloid Leukemia ◽  
Posttranslational Modifications ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Genetic Alterations ◽  
Loss Of Function ◽  
Epigenetic Modifiers ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Recent studies of the spectrum of somatic genetic alterations in acute myeloid leukemia (AML) have identified frequent somatic mutations in genes that encode proteins important in the epigenetic regulation of gene transcription. This includes proteins involved in the modification of DNA cytosine residues and enzymes which catalyze posttranslational modifications of histones. Here we describe the clinical, biological, and therapeutic relevance of mutations in epigenetic regulators in AML. In particular, we focus on the role of loss-of-function mutations in TET2, gain-of-function mutations in IDH1 and IDH2, and loss-of-function mutations in ASXL1 and mutations of unclear impact in DNMT3A in AML pathogenesis and therapy. Multiple studies have consistently identified that mutations in these genes have prognostic relevance, particularly in intermediate-risk AML patients, arguing for inclusion of mutational testing of these genetic abnormalities in routine clinical practice. Moreover, biochemical, biological, and epigenomic analyses of the effects of these mutations have informed the development of novel therapies which target pathways deregulated by these mutations. Our understanding of the effects of these mutations on hematopoiesis and potential for therapeutic targeting of specific AML subsets is also reviewed here.

Development of Squamous Cell Carcinoma of the Tongue during Induction Chemotherapy for Acute Myeloid Leukemia

2005 ◽  
Vol 91 (1) ◽  
pp. 81-83 ◽  
Author(s):  
Ali Ugur Ural ◽  
Ferit Avcu ◽  
Mahmut Ilker Yilmaz ◽  
Metin Guden ◽  
Bekir Ozturk ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Medical Literature ◽  
Squamous Cell Carcinomas ◽  
The Third ◽  
Acute Myeloid

Immunosuppression is a well-recognized cause of skin tumors, in particular squamous cell carcinomas (SCC). In patients with hematological malignancies undergoing chemotherapy, SCC has been reported late in the course of the disease or many years after completion of treatment. Here we report a patient with acute myeloid leukemia who developed a SCC of the tongue while receiving the third course of induction chemotherapy. This is the second such case in the medical literature. The role of immunosuppression, chemotherapy, the malignancy itself and possible genetic predisposition is discussed and the literature on this topic is reviewed.

scholarly journals Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3941
Author(s):  
Lennart Beckmann ◽  
Christina Charlotte Rolling ◽  
Minna Voigtländer ◽  
Jonathan Mäder ◽  
Felix Klingler ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tissue Factor ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Reductase Activity ◽  
Exchange Reactions ◽  
Aberrant Expression ◽  
Inflammatory Monocytes ◽  
Acute Myeloid

Aberrant expression of tissue factor (TF) by transformed myeloblasts and inflammatory monocytes drives coagulation activation in acute myeloid leukemia (AML). Although regulation of TF procoagulant activity (PCA) involves thiol-disulfide exchange reactions, the specific role of protein disulfide isomerase (PDI) and other thiol isomerases in AML-associated TF biology is unclear. THP1 cells and peripheral blood mononuclear cells (PBMCs) from healthy controls or AML patients were analyzed for thiol isomerase-dependent TF production under various experimental conditions. Total cellular and membrane TF antigen, TF PCA and TF mRNA were analyzed by ELISA, flow cytometry, clotting or Xa generation assay and qPCR, respectively. PBMCs and THP1 cells showed significant insulin reductase activity, which was inhibited by bacitracin or rutin. Co-incubation with these thiol isomerase inhibitors prevented LPS-induced TF production by CD14-positive monocytes and constitutive TF expression by THP1 cells and AML blasts. Downregulation of the TF antigen was mainly restricted to the cryptic pool of TF, efficiently preventing phosphatidylserine-dependent TF activation by daunorubicin, and at least partially regulated on the mRNA level in LPS-stimulated monocytes. Our study thus delineates a complex role of thiol isomerases in the regulation of myeloid TF PCA, with PDI being a promising therapeutic target in the management of AML-associated coagulopathies.

scholarly journals Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia

Blood ◽  
2016 ◽  
Vol 127 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Bas J. Wouters ◽  
Ruud Delwel
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Common Type ◽  
Targeted Treatment ◽  
Epigenetic Therapy ◽  
Genetic Changes ◽  
Current State ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. AML is a heterogeneous malignancy characterized by distinct genetic abnormalities. Recent discoveries have highlighted an additional important role of dysregulated epigenetic mechanisms in the pathogenesis of the disease. In contrast to genetic changes, epigenetic modifications are frequently reversible, which provides opportunities for targeted treatment using specific inhibitors. In this review, we will provide an overview of the current state of epigenetics and epigenetic therapy in AML and will describe perspectives on how to identify promising new approaches for epigenetic targeted treatment.

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid

scholarly journals Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yiyi Yao ◽  
Fenglin Li ◽  
Jiansong Huang ◽  
Jie Jin ◽  
Huafeng Wang
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chemotherapy Resistance ◽  
Bone Marrow Microenvironment ◽  
Cytotoxic Effects ◽  
High Relapse Rate ◽  
Underlying Mechanisms ◽  
Acute Myeloid

AbstractDespite the advances in intensive chemotherapy regimens and targeted therapies, overall survival (OS) of acute myeloid leukemia (AML) remains unfavorable due to inevitable chemotherapy resistance and high relapse rate, which mainly caused by the persistence existence of leukemia stem cells (LSCs). Bone marrow microenvironment (BMM), the home of hematopoiesis, has been considered to play a crucial role in both hematopoiesis and leukemogenesis. When interrupted by the AML cells, a malignant BMM formed and thus provided a refuge for LSCs and protecting them from the cytotoxic effects of chemotherapy. In this review, we summarized the alterations in the bidirectional interplay between hematopoietic cells and BMM in the normal/AML hematopoietic environment, and pointed out the key role of these alterations in pathogenesis and chemotherapy resistance of AML. Finally, we focused on the current potential BMM-targeted strategies together with future prospects and challenges. Accordingly, while further research is necessary to elucidate the underlying mechanisms behind LSC–BMM interaction, targeting the interaction is perceived as a potential therapeutic strategy to eradicate LSCs and ultimately improve the outcome of AML.

scholarly journals High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Li ◽  
Zheng Ge
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Cell Function ◽  
Adverse Outcomes ◽  
High Expression ◽  
Micro Rnas ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA). Conclusions Our research revealed HSPA8 as a novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with the HSPA8 high expression in AML.

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