Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia

2012 ◽  
Vol 13 (3) ◽  
pp. 269-282 ◽  
Author(s):  
Ajay Abraham ◽  
Savitha Varatharajan ◽  
Salar Abbas ◽  
Wei Zhang ◽  
Ramachandran V Shaji ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Genetic Variants ◽  
Myeloid Leukemia ◽  
Cytidine Deaminase ◽  
Rna Expression ◽  
Acute Myeloid

scholarly journals Functional implications of microRNAs in acute myeloid leukemia by integrating microRNA and messenger RNA expression profiling

Cancer ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 4696-4706 ◽  
Author(s):  
Violaine Havelange ◽  
Nicole Stauffer ◽  
Catherine C. E. Heaphy ◽  
Stefano Volinia ◽  
Michael Andreeff ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Expression Profiling ◽  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Rna Expression ◽  
Functional Implications ◽  
Rna Expression Profiling ◽  
Acute Myeloid

Increased Frequency of Fanconi Anemia Group C Genetic Variants in Children With Sporadic Acute Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4813-4814 ◽  
Author(s):  
Abida Awan ◽  
G. Malcolm Taylor ◽  
David A. Gokhale ◽  
Simon P. Dearden ◽  
Andrew Will ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Fanconi Anemia ◽  
Genetic Variants ◽  
Myeloid Leukemia ◽  
Anemia Group ◽  
Acute Myeloid

Immunogenicity and Antileukemic Activity of Dendritic Cells Electroporated with Wilms’ Tumor WT1 mRNA: A Phase I/II Trial in Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 830-830 ◽  
Author(s):  
Zwi N. Berneman ◽  
Ann Van de Velde ◽  
Ann Van Driessche ◽  
Nathalie Cools ◽  
Barbara Stein ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Rna Expression ◽  
Antileukemic Activity ◽  
Dc Vaccines ◽  
Acute Myeloid

Abstract The Wilms’ tumor protein WT1 is a target for immunotherapy in malignancies, such as acute myeloid leukemia (AML). Following our demonstration that dendritic cells (DC) can be efficiently transfected by messenger (m)RNA electroporation (Van Tendeloo VF et al. Blood2001;98:49–56) and that WT1 mRNA-electroporated DC stimulate WT1-specific T cells in vitro (Van Driessche A et al. Leukemia2005;19:1863–1871), we performed a phase I/II dose-escalation trial, in which patients with AML in remission but at high risk of relapse and without a direct sib allo-transplant option (9 patients) or with slowly progressive AML (1 patient) received intradermal injections of WT1 RNA-loaded DC. Following apheresis and CD14 immunomagnetic monocyte separation, DC were generated in 6-day cultures in clinical-grade medium supplemented with serum, granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, matured with prostaglandin (PG)E2 and tumor necrosis factor (TNF)-alpha, harvested, electroporated with WT1 mRNA and used as vaccines. The patients received four biweekly DC vaccines and a delayed-type hypersensitivity (DTH) test was performed 2 weeks following the last vaccination. Patients were monitored for minimal residual disease (MRD) by analyzing WT1 RNA expression in peripheral blood by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) (Cilloni D et al. Leukemia2002;16:2115–2121 & Cilloni D et al. Haematologica2008;93:921–924). Before and after vaccination, peripheral blood was collected for immunomonitoring purposes. Feasibility, safety, immunogenicity and effect on MRD were investigated. There was successful DC generation and vaccine production in all 10 patients. No serious adverse events or toxicity were observed and vaccinations were well tolerated. A decrease in WT1 RNA expression was observed during the course of the vaccination in 4/7 patients who had an increased WT1 mRNA level in peripheral blood. Three of those patients are still in complete hematological remission. An in vivo vaccine-specific immune response was demonstrated in 10/10 patients by DTH. Ex vivo immunomonitoring analysis showed a significant increase in circulating activated HLA-DR+ CD4+ T cells and in IL-2 plasma levels following vaccination. Importantly, in vitro restimulation assays of peripheral blood mononuclear cells revealed a significant postvaccination increase in interferon (IFN)-gamma-producing WT1-specific CD8+ T cells (n= 8 evaluable patients), but not in cytokine-producing WT1-specific CD4+ T cells. There was no significant change in WT1-specific antibodies following vaccination. We conclude that vaccination of AML patients with WT1 RNA-loaded DC is feasible and safe. Furthermore, the DC elicit vaccine-specific and WT1-specific CD8+ T-cell responses. The correlation between reduction of circulating WT1 mRNA and the administration of the DC vaccines strongly suggests that this DC vaccine elicits an antileukemic activity.

ABCB6 RNA expression in leukemias—expression is low in acute promyelocytic leukemia and FLT3-ITD-positive acute myeloid leukemia

2013 ◽  
Vol 93 (3) ◽  
pp. 509-512 ◽  
Author(s):  
Ajay Abraham ◽  
Sreeja Karathedath ◽  
Savitha Varatharajan ◽  
Preetha Markose ◽  
Ezhilarasi Chendamarai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
Promyelocytic Leukemia ◽  
Rna Expression ◽  
Acute Myeloid

scholarly journals Clinical and molecular relevance of genetic variants in the non-coding transcriptome of patients with cytogenetically normal acute myeloid leukemia

Haematologica ◽  
2021 ◽  
Author(s):  
Dimitrios Papaioannou ◽  
Hatice G. Ozer ◽  
Deedra Nicolet ◽  
Amog P. Urs ◽  
Tobias Herold ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Rna Sequencing ◽  
Clinical Significance ◽  
Genetic Variants ◽  
Myeloid Leukemia ◽  
Sequencing Data ◽  
Younger Adults ◽  
Non Coding Rnas ◽  
Acute Myeloid

Expression levels of long non-coding RNAs (lncRNAs) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNAs in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged

scholarly journals Lower RNA expression of ALDH1A1 distinguishes the favorable risk group in acute myeloid leukemia

2021 ◽  
Author(s):  
Garrett M. Dancik ◽  
Ioannis F. Voutsas ◽  
Spiros A. Vlahopoulos
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Tyrosine Kinases ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Rna Expression ◽  
Poor Overall Survival ◽  
Activity Of Enzymes ◽  
Acute Myeloid

The expression and activity of enzymes that belong to the aldehyde dehydrogenases is a characteristic of both normal and malignant stem cells. ALDH1A1 is an enzyme critical in cancer stem cells. In acute myeloid leukemia (AML), ALDH1A1 protects leukemia-initiating cells from a number of antineoplastic agents, which include inhibitors of protein tyrosine kinases. Furthermore, ALDH1A1 proves vital for the establishment of human AML xenografts in mice. We review here important studies characterizing the role of ALDH1A1 in AML and its potential as a therapeutic target. We also analyze datasets from leading studies, and show that decreased ALDH1A1 RNA expression consistently characterizes the AML patient risk group with a favorable prognosis, while there is a consistent association of high ALDH1A1 RNA expression with high risk and poor overall survival. Our review and analysis reinforces the notion to employ both novel as well as existing inhibitors of the ALDH1A1 protein against AML.

scholarly journals RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia

2015 ◽  
Vol 16 (8) ◽  
pp. 877-890 ◽  
Author(s):  
Ajay Abraham ◽  
Savitha Varatharajan ◽  
Sreeja Karathedath ◽  
Chepsy Philip ◽  
Kavitha M Lakshmi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Rna Expression ◽  
Expression Of Genes ◽  
Acute Myeloid
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