scholarly journals A Role for Lipid Mediators in Acute Myeloid Leukemia

2019 ◽  
Vol 20 (10) ◽  
pp. 2425 ◽  
Author(s):  
Andreas Loew ◽  
Thomas Köhnke ◽  
Emma Rehbeil ◽  
Anne Pietzner ◽  
Karsten-H. Weylandt
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Therapy ◽  
Hematologic Malignancies ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Immune Mechanisms ◽  
Acute Myeloid

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.

Mechanisms of Suppression Used by Regulatory T Cells in Patients Newly Diagnosed with Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2938-2938 ◽  
Author(s):  
Miroslaw J Szczepanski ◽  
Marta Szajnik ◽  
Malgorzata Czystowska ◽  
Magis Mandapathil ◽  
Ann Welsh ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Regulatory T Cells ◽  
Myeloid Leukemia ◽  
Neutralizing Antibodies ◽  
Hematologic Malignancies ◽  
Cell Contact ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract An elevated frequency of CD4+CD25high regulatory T cells (Treg) has been reported in the peripheral blood in patients with various solid tumors and hematologic malignancies. Although the increase in Treg seems to be a characteristic feature of most tumors, the functional role of Treg and the mechanisms of suppression, especially in patients with hematologic malignancies, have been less well defined. We investigated Treg-mediated suppression and the responsible mechanisms in thirty newly diagnosed acute myeloid leukemia (AML) patients prior to any treatment and twenty five healthy donors (NC). The percentage of circulating CD4+ CD25high Treg was higher (p <0.0001) in the AML patients (4.5 ±0.2%, range 1.7–8.2%) compared to NC (1.5 ± 0.08%, range 0.9–3.1 %). To evaluate the suppressive function, CD4+CD25high T cells (S) were co-cultured with sorted, CFSE-labeled autologous CD4+CD25high T cells (R) at different S/R ratios. Suppression mediated by Treg co-incubated with proliferating autologous responders was significantly higher (p<0.001) in AML than that mediated by control Treg. To evaluate the role of cytokines produced by Treg in suppression and a need for cell-to- cell contact, transwell analysis of S/R co-cultures was performed. Co-incubation in the presence of transwell inserts (TRI) resulted in significant reduction of suppression (p<0.05), and the addition of neutralizing antibodies to IL-10 and TGF-β1 in the presence of TRI further decreased suppression mediated by Treg. These data suggest that both immunoinhibitory cytokine production and cell-to-cell contact are necessary for suppression. To explore other potential mechanisms of Treg suppression, we evaluated the expression by Treg of ectonucleotidases CD39 and CD73 and the capability of Treg to produce adenosine. CD4+CD25high T cells of AML patients had higher expression (p<0.01) of CD39 and more efficiently hydrolyzed ATP to adenosine relative to Treg in NC. These data indicate that various mechanisms of suppression may be utilized by Treg in patients with AML. The increase frequency of Treg mediating potent suppression by various mechanisms is likely to play a role in host anti-tumor immune responses. Therefore, modulation of the frequency and functions of Treg might provide new immunotherapeutic approaches in AML.

scholarly journals Measurable Residual Disease in Acute Myeloid Leukemia Using Flow Cytometry: A Review of Where We Are and Where We Are Going

2020 ◽  
Vol 9 (6) ◽  
pp. 1714
Author(s):  
Caroline Dix ◽  
Tsun-Ho Lo ◽  
Georgina Clark ◽  
Edward Abadir
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Hematologic Malignancies ◽  
Leukemic Cells ◽  
Prognostic Models ◽  
Measurable Residual Disease ◽  
Acute Myeloid

The detection of measurable residual disease (MRD) has become a key investigation that plays a role in the prognostication and management of several hematologic malignancies. Acute myeloid leukemia (AML) is the most common acute leukemia in adults and the role of MRD in AML is still emerging. Prognostic markers are complex, largely based upon genetic and cytogenetic aberrations. MRD is now being incorporated into prognostic models and is a powerful predictor of relapse. While PCR-based MRD methods are sensitive and specific, many patients do not have an identifiable molecular marker. Immunophenotypic MRD methods using multiparametric flow cytometry (MFC) are widely applicable, and are based on the identification of surface marker combinations that are present on leukemic cells but not normal hematopoietic cells. Current techniques include a “different from normal” and/or a “leukemia-associated immunophenotype” approach. Limitations of MFC-based MRD analyses include the lack of standardization, the reliance on a high-quality marrow aspirate, and variable sensitivity. Emerging techniques that look to improve the detection of leukemic cells use dimensional reduction analysis, incorporating more leukemia specific markers and identifying leukemic stem cells. This review will discuss current methods together with new and emerging techniques to determine the role of MFC MRD analysis.

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 Role of CD19 and specific KIT‐D816 on risk stratification refinement in t(8;21) acute myeloid leukemia induced with different cytarabine intensities

2020 ◽  
Author(s):  
Biao Wang ◽  
Bin Yang ◽  
Yun Ling ◽  
Jihong Zhang ◽  
Xiaoying Hua ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Acute Myeloid

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.

The role of PRDM16 and its isoforms in acute myeloid leukemia

2016 ◽  
Vol 44 (9) ◽  
pp. S65 ◽  
Author(s):  
David Corrigan ◽  
Larry Luchsinger ◽  
Hans Snoeck
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Ginsenoside 20(S)-Rh2 Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells: Role of Orphan Nuclear Receptor Nur77

2017 ◽  
Vol 65 (35) ◽  
pp. 7687-7697 ◽  
Author(s):  
Chengqiang Wang ◽  
Hui He ◽  
Guojun Dou ◽  
Juan Li ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Nuclear Receptor ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Orphan Nuclear Receptor ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

scholarly journals Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of miR-26a and Histone Methyltransferase EZH2

2011 ◽  
Vol 2 (5) ◽  
pp. 585-592 ◽  
Author(s):  
B. Salvatori ◽  
I. Iosue ◽  
N. Djodji Damas ◽  
A. Mangiavacchi ◽  
S. Chiaretti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Histone Methyltransferase ◽  
Direct Regulation ◽  
Acute Myeloid
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