scholarly journals Using Circ-ANAPC7 as a Novel Type of Biomarker in the Monitoring of Acute Myeloid Leukemia

2021 ◽  
pp. 1-7
Author(s):  
Ying Shen ◽  
Yachun Jia ◽  
Ru Zhang ◽  
Hongli Chen ◽  
Yuandong Feng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Roc Curve ◽  
Myeloid Leukemia ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Roc Curve Analysis ◽  
Cell Counts ◽  
Acute Myeloid

<b><i>Introduction:</i></b> Circular RNAs (circRNAs) are a novel class of RNAs which occupy gene expression at the transcriptional or post-transcriptional level, involve in many physiological processes, and participate in many diseases, especially in cancer. Our previous study showed 1 altered circRNA named circ-anaphase promoting complex subunit 7 (ANAPC7) that was upregulated in acute myeloid leukemia (AML). To further clear the expression and clinical significance of circ-ANAPC7, we enlarged the sample size and illuminated the diagnostic and monitoring value of circ-ANAPC7 in AML. <b><i>Methods:</i></b> Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was supposed to confirm the expression of circ-ANAPC7 of AML patients. We assessed the correlation of circ-ANAPC7 and clinical variables using the Spearman correlation test. The receiver operating characteristic (ROC) curve was carried out to evaluate the diagnostic value. <b><i>Results:</i></b> Circ-ANAPC7 was first found to be upregulated in AML, and its expression was correlated to white blood cell counts in peripheral blood and blast percentage in bone marrow. ROC curve analysis revealed that circ-ANAPC7 has a significant value of auxiliary AML diagnosis (area under the curve = 0.915, <i>p</i> &#x3c; 0.001). Furthermore, the expression level of circ-ANAPC7 was changed accompanied with disease condition transformation. <b><i>Conclusion:</i></b> Circ-ANAPC7 was upregulated in newly diagnosed and relapsed AML. It may serve as potential biomarkers for AML patient’s diagnosis and monitoring.

scholarly journals Using circ-ANAPC7 as a novel type of biomarker in the monitoring of acute myeloid leukemia

2020 ◽  
Author(s):  
Ying Shen ◽  
Yachun Jia ◽  
Ru Zhang ◽  
Hongli Chen ◽  
Ting Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Roc Curve ◽  
Myeloid Leukemia ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Roc Curve Analysis ◽  
Disease Condition ◽  
Spearman Correlation Test ◽  
Acute Myeloid

Abstract Background Circular RNAs (circRNAs) that occupy gene expression at the transcriptional or post-transcriptional level have great potential to be biomarker for types of cancers. We have screened one altered circRNA named circ-ANAPC7 in acute myeloid leukemia (AML) before. In this study, we aimed to validate its expression by enlarging sample size and illuminating the diagnostic and monitoring value of circ-ANAPC7 in AML. Methods Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was supposed to confirm the expression of circ-ANAPC7 of AML patients. We assessed the correlation of circ-ANAPC7 and clinical variables using Spearman correlation test. Receiver operating characteristic (ROC) curve was carried out to evaluate the diagnostic value. Results Circ-ANAPC7 was first found to be upregulated in AML, and its expression was correlated to WBC counts and blast percentage in bone marrow. ROC curve analysis revealed that circ-ANAPC7 has significant value of AML diagnosis (AUC = 0.915, P < 0.001). Furthermore, the expression level of circ-ANAPC7 was changed accompanied with disease condition transformation. Conclusions Circ-ANAPC7 could be used as a biomarker to monitor disease condition of AML.

scholarly journals CircRNF220, not its linear cognate gene RNF220, regulates cell growth and is associated with relapse in pediatric acute myeloid leukemia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaodan Liu ◽  
Xiaoping Liu ◽  
Mansi Cai ◽  
Ailing Luo ◽  
Yingyi He ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
High Sensitivity ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Transcriptional Networks ◽  
Pediatric Acute Myeloid Leukemia ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract Background Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and have been confirmed to be critical in tumorigenesis and to be potential biomarkers or therapeutic targets. However, only a few circRNAs have been functionally characterized in pediatric acute myeloid leukemia (AML). Methods Here, we investigated the expression pattern of circRNAs in pediatric AML using a circRNA microarray. The characteristics, potential diagnostic value, and prognostic significance of circRNF220 were evaluated. A series of functional experiments were performed to investigate the role of circRNF220 in primary pediatric AML cells. Then we investigated the aberrant transcriptional networks regulated by circRNF220 in primary AML cells by RNA-seq. Furthermore, biotin RNA pulldown assays were implemented to verify the relationship between circRNF220 and miR-30a. Results We identified a circRNA, circRNF220, which was specifically abundant in and accumulated in the peripheral blood and bone marrow of pediatric patients with AML. It could distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity. Significantly, circRNF220 expression independently predicted prognosis, while high expression of circRNF220 was an unfavorable prognostic marker for relapse. Furthermore, we characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibited proliferation and promoted apoptosis in AML cell lines and primary cells. Mechanistically, circRNF220 may act as an endogenous sponge of miR-30a to sequester miR-30a and inhibit its activity, which increases the expression of its targets MYSM1 and IER2 and implicated in AML relapse. Conclusions Collectively, these findings demonstrated that circRNF220 could be highly efficient and specific for the accurate diagnosis of pediatric AML, with implications for relapse prediction.

scholarly journals High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 3091-3096 ◽  
Author(s):  
L Campos ◽  
JP Rouault ◽  
O Sabido ◽  
P Oriol ◽  
N Roubi ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mitochondrial Protein ◽  
High Expression ◽  
Leukemic Cells ◽  
Stem Cell Marker ◽  
Cell Counts ◽  
Response To Chemotherapy ◽  
Acute Myeloid

The BCL-2 proto-oncogene encodes a mitochondrial protein that blocks programmed cell death. High amounts of bcl-2 protein are found not only in lymphoid malignancies, but also in normal tissues characterized by apoptotic cell death, including bone marrow. Using a monoclonal antibody to bcl-2 protein, we analyzed 82 samples of newly diagnosed acute myeloid leukemia. The number of bcl-2+ cells in each sample was heterogeneous (range, 0% to 95%), with a mean of 23%. The percentage of bcl-2+ cells was higher in M4 and M5 types, according to French- American-British classification, and in cases with high white blood cell counts. bcl-2 expression was also correlated with that of the stem cell marker CD34. In vitro survival of leukemic cells maintained in liquid culture in the absence of growth factors was significantly longer in cases with a high percentage of bcl-2+ cells. High expression of bcl-2 was associated with a low complete remission rate after intensive chemotherapy (29% in cases with 20% or more positive cells v 85% in cases with less than 20% positive cells, P < 10(-5)) and with a significantly shorter survival. In multivariate analysis, the percentage of bcl-2+ cells (or the blast survival in culture), age, and the percentage of CD34+ cells were independently associated with poor survival.

scholarly journals Circular RNAs in Hematopoiesis with a Focus on Acute Myeloid Leukemia and Myelodysplastic Syndrome

2020 ◽  
Vol 21 (17) ◽  
pp. 5972
Author(s):  
Michaela Dostalova Merkerova ◽  
Zdenek Krejcik ◽  
Katarina Szikszai ◽  
David Kundrat
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Experimental Methods ◽  
Circular Rnas ◽  
Specific Expression ◽  
Hematopoietic Stem ◽  
Recent Developments ◽  
Disease Specific ◽  
Acute Myeloid

Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs. However, despite the growing number of circRNAs described to date, the roles of the majority of them in hematopoiesis remain unknown. Given their stability and disease-specific expression, circRNAs have been acknowledged as novel promising biomarkers and therapeutic targets. In this paper, the biogenesis, characteristics, and roles of circRNAs are reviewed with an emphasis on their currently recognized or presumed involvement in hematopoiesis, especially in acute myeloid leukemia and myelodysplastic syndrome.

scholarly journals Gpr44 Mediates the Selenium-Dependent Anti-Leukemic Effect in Acute Myeloid Leukemia

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1835-1835
Author(s):  
Fenghua Qian ◽  
Fenghua Qian ◽  
Diwakar Tukaramrao ◽  
Jiayan Zhou ◽  
Nicole Palmiero ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Murine Model ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Pparγ Agonist ◽  
Acute Myeloid

Abstract Objectives The relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia stem cells (LSCs) that are not targeted by existing therapies. LSCs show sensitivity to endogenous cyclopentenone prostaglandin J (CyPG) metabolites that are increased by dietary trace element selenium (Se), which is significantly decreased in AML patients. We investigated the anti-leukemic effect of Se supplementation in AML via mechanisms involving the activation of the membrane-bound G-protein coupled receptor 44 (Gpr44) and the intracellular receptor, peroxisome proliferator-activated receptor gamma (PPARγ), by endogenous CyPGs. Methods A murine model of AML generated by transplantation of hematopoietic stem cells (HSCs- WT or Gpr44−/−) expressing human MLL-AF9 fusion oncoprotein, in the following experiments: To investigate the effect of Se supplementation on the outcome of AML, donor mice were maintained on either Se-adequate (Se-A; 0.08–0.1 ppm Se) or Se-supplemented (Se-S; 0.4 ppm Se) diets. Complete cell counts in peripheral blood were analyzed by hemavet. LSCs in bone marrow and spleen were analyzed by flow cytometry. To determine the role of Gpr44 activation in AML, mice were treated with Gpr44 agonists, CyPGs. LSCs in bone marrow and spleen were analyzed. Mice transplanted with Gpr44−/- AML cells were compared with mice transplanted with wild type AML cells and the progression of the disease was followed as above. To determine the role of PPARγ activation in AML, PPARγ agonist (Rosiglitazone, 6 mg/kg, i.p, 14 d) and antagonist (GW9662, 1 mg/kg, i.p. once every other day, 7 injections) were applied to Se-S mice transplanted with Gpr44−/- AML cells and disease progression was followed. Results Se supplementation at supraphysiological levels alleviated the disease via the elimination of LSCs in a murine model of AML. CyPGs induced by Se supplementation mediate the apoptosis in LSCs via the activation of Gpr44 and PPARγ. Conclusions Endogenous CyPGs produced upon supplementation with Se at supraphysiological levels improved the outcome of AML by targeting LSCs to apoptosis via the activation of two receptors, Gpr44 and PPARg. Funding Sources NIH DK 07,7152; CA 175,576; CA 162,665. Office of Dietary Supplements, USDA Hatch funds PEN04605, Accession # 1,010,021 (KSP, RFP).

scholarly journals MicroRNA-181a-3p as a diagnostic and prognostic biomarker for acute myeloid leukemia

2020 ◽  
Vol 12 (1) ◽  
pp. e2020012
Author(s):  
Xiaoling Ma
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Disease Marker ◽  
Blood Specimens ◽  
Cox Analysis ◽  
Acute Myeloid

Background: Micro (mi)RNAs play an important role in the pathogenesis and development of acute myeloid leukemia (AML), and their abnormal expression may be sufficient to predict the prognosis and outcomes in AML patients. We evaluated the clinical diagnostic value of miRNA-181a-3p in predicting prognosis and outcomes in patients with AML. Methods: A total of 119 newly diagnosed adult patients with AML and 60 healthy controls were recruited. Blood specimens were obtained from all AML patients at diagnosis, and 10 blood specimens were obtained on day 28 after induction chemotherapy. The controls also provided blood samples. MiR-181a-3p expression was quantified by PCR, and relative miRNA expression was determined using the comparative Ct method. Results: Compared with healthy controls, the expression of miRNA-181a-3p was significantly increased in patients with AML. MiR-181a-3p expression could be used to discriminate AML patients from controls, with up-regulated expression correlating with favorable prognosis. Moreover, miRNA-181a-3p expression was significantly decreased in patients who achieved a complete response after induction chemotherapy. The multivariate Cox analysis highlighted the prognostic value of miR-181a-3p for patients with AML. Conclusions: MiR-181a-3p may be clinically useful as a disease marker for AML, and enhanced the prediction of patient outcomes to chemotherapy.

scholarly journals hsa_circ_0001947 suppresses acute myeloid leukemia progression via targeting hsa-miR-329-5p/CREBRF axis

Epigenomics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 935-953 ◽  
Author(s):  
Fengjiao Han ◽  
Chaoqin Zhong ◽  
Wei Li ◽  
Ruiqing Wang ◽  
Chen Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cancer Biology ◽  
Circular Rnas ◽  
Reverse Transcription Pcr ◽  
Potential Biomarker ◽  
Differential Expression Profile ◽  
Acute Myeloid

Aim: Accumulating evidence has indicated that circular RNAs (circRNAs) are involved in cancer biology. However, their roles in acute myeloid leukemia (AML) remain unclear. Therefore, we aimed to define novel circRNAs involved the development and progression of AML. Materials & methods: We used circRNAs microarray to determine the differential expression profile. Quantitative reverse transcription PCR analyzed the expression of hsa_circ_0001947. The siRNA assesses the function of hsa_circ_0001947 in vitro and in vivo. A dual-luciferase and mimics/inhibitor were to determine the target gene relationship. Results: hsa_circ_0001947 functions as a tumor inhibitor to suppress AML cell proliferation through hsa-miR-329-5p/ CREBRF axis. Conclusion: hsa_circ_0001947 may be as a novel potential biomarker for the treatment of AML.

scholarly journals High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 3091-3096 ◽  
Author(s):  
L Campos ◽  
JP Rouault ◽  
O Sabido ◽  
P Oriol ◽  
N Roubi ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mitochondrial Protein ◽  
High Expression ◽  
Leukemic Cells ◽  
Stem Cell Marker ◽  
Cell Counts ◽  
Response To Chemotherapy ◽  
Acute Myeloid

Abstract The BCL-2 proto-oncogene encodes a mitochondrial protein that blocks programmed cell death. High amounts of bcl-2 protein are found not only in lymphoid malignancies, but also in normal tissues characterized by apoptotic cell death, including bone marrow. Using a monoclonal antibody to bcl-2 protein, we analyzed 82 samples of newly diagnosed acute myeloid leukemia. The number of bcl-2+ cells in each sample was heterogeneous (range, 0% to 95%), with a mean of 23%. The percentage of bcl-2+ cells was higher in M4 and M5 types, according to French- American-British classification, and in cases with high white blood cell counts. bcl-2 expression was also correlated with that of the stem cell marker CD34. In vitro survival of leukemic cells maintained in liquid culture in the absence of growth factors was significantly longer in cases with a high percentage of bcl-2+ cells. High expression of bcl-2 was associated with a low complete remission rate after intensive chemotherapy (29% in cases with 20% or more positive cells v 85% in cases with less than 20% positive cells, P < 10(-5)) and with a significantly shorter survival. In multivariate analysis, the percentage of bcl-2+ cells (or the blast survival in culture), age, and the percentage of CD34+ cells were independently associated with poor survival.

Antigen Expression Varies Significantly between Molecular Subgroups of Acute Myeloid Leukemia Patients: Clinical Applicability Is Hampered by Establishment of Relevant Cutoffs

2020 ◽  
pp. 1-10
Author(s):  
Laura Laine Herborg ◽  
Line Nederby ◽  
Rasmus Froberg Brøndum ◽  
Maria Hansen ◽  
Peter Hokland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Area Under The Curve ◽  
Antigen Expression ◽  
Operating Characteristics ◽  
Exact Test ◽  
Clinical Applicability ◽  
Mutational Status ◽  
Type Gene ◽  
Acute Myeloid

<b><i>Introduction:</i></b> In this single-center study of 268 acute myeloid leukemia (AML) patients, we have tested if a subset of 4 routinely employed immunophenotypic stem cell-associated markers correlated with the presence of recurrently mutated genes and if the markers were predictive for mutational status. <b><i>Methods:</i></b> Immunophenotypic data from 268 diagnostic AML samples obtained in 2009–2018 were analyzed retrospectively for the antigens CD34, CD117, CD123, and CLEC12A. Correlation between immunophenotypes and mutations was analyzed by Fischer’s exact test. Clinical applicability of the markers for predicting mutational status was evaluated by receiver operating characteristics analyses, where an area under the curve (AUC) of at least 0.85 was accepted as clinically relevant. <b><i>Results:</i></b> For a number of genes, the antigen expression differed significantly between mutated and wild-type gene expression. Despite low AUCs, CD123 and CLEC12A correlated with <i>FLT3</i>+<i>NPM1−</i> and <i>FLT3</i>+<i>NPM1</i>+. Three subsets met the AUC requirements (CD34+, CD34+CD117+, and CD34−CD117+) for predicting <i>FLT3−NPM1</i>+ or <i>FLT3</i>+<i>NPM1</i>+. <b><i>Conclusion:</i></b> The value of immunophenotypes as surrogate markers for mutational status in AML seems limited when employing CD123 and CLEC12A in combination with CD34 and CD117. Defining relevant cutoffs for given markers is challenging and hampered by variation between laboratories and patient groups.

scholarly journals Age and acute myeloid leukemia

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3481-3485 ◽  
Author(s):  
Frederick R. Appelbaum ◽  
Holly Gundacker ◽  
David R. Head ◽  
Marilyn L. Slovak ◽  
Cheryl L. Willman ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Group Treatment ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Poor Performance ◽  
The Elderly ◽  
Lower Percentage ◽  
Poor Performance Status ◽  
Cell Counts ◽  
Acute Myeloid

We conducted a retrospective analysis of 968 adults with acute myeloid leukemia (AML) on 5 recent Southwest Oncology Group trials to understand how the nature of AML changes with age. Older study patients with AML presented with poorer performance status, lower white blood cell counts, and a lower percentage of marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger than age 56 compared with 57% in patients older than 75. The percentage of patients with favorable cytogenetics dropped from 17% in those younger than age 56 to 4% in those older than 75. In contrast, the proportion of patients with unfavorable cytogenetics increased from 35% in those younger than age 56 to 51% in patients older than 75. Particularly striking were the increases in abnormalities of chromosomes 5, 7, and 17 among the elderly. The increased incidence of unfavorable cytogenetics contributed to their poorer outcome, and, within each cytogenetic risk group, treatment outcome deteriorated markedly with age. Finally, the combination of a poor performance status and advanced age identified a group of patients with a very high likelihood of dying within 30 days of initiating induction therapy. The distinct biology and clinical responses seen argue for age-specific assessments when evaluating therapies for AML.

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