In Silico Identification of Novel Acute Myeloid Leukemia Associated Missense SNPs in Human CEBPA Gene

2020 ◽  
pp. 10-24
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Silico ◽  
Myeloid Leukemia ◽  
Gene Interaction ◽  
Nucleotide Polymorphisms ◽  
Future Perspectives ◽  
Single Nucleotide ◽  
In Silico Identification ◽  
And Function ◽  
Acute Myeloid

Single nucleotide polymorphisms (SNPs) in CEBPA gene have been found to be associated with cancer especially Acute Myeloid Leukemia (AML). Therefore, the identification of functional and structural polymorphisms in CEBPA is important to study and discover therapeutics targets and potential malfunctioning. For this purpose, several bioinformatics tools were used for the identification of disease-associated nsSNPs, which might be vital for the structure and function of CEBPA, making them extremely important. In silico tools used in this study included SIFT, PROVEAN, PolyPhen2, SNP&GO and PhD-SNP, followed by ConSurf and I-Mutant. Protein 3D modelling was carried out using I-TASSER and MODELLER v9.22, while GeneMANIA and string were used for the prediction of gene-gene interaction in this regard. From our study, we found that the L345P, R333C, R339Q, V328G, R327W, L317Q, N292S, E284A, R156W, Y108N and F82L mutations were the most crucial SNPs. Additionally, the gene-gene interaction showed the genes having correlation with CEBPA’s co-expressions and importance in several pathways. In future, these 11 mutations should be investigated while studying diseases related to CEBPA, especially for AML. Being the first of its kind, future perspectives are proposed in this study, which will help in precision medicine. Animal models are of great significance in finding out CEBPA effects in disease.

IL-17 A and IL-17 F single nucleotide polymorphisms and acute myeloid leukemia susceptibility and response to induction therapy in Egypt

Meta Gene ◽  
2020 ◽  
Vol 26 ◽  
pp. 100773
Author(s):  
Rania A. Zayed ◽  
Zainab El-Saadany ◽  
Hanan Nour Raslan ◽  
Mohammed Ghareeb ◽  
Dalia Ibraheem ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Acute Myeloid

scholarly journals Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Barbara-ann Guinn ◽  
Azim Mohamedali ◽  
Ken I. Mills ◽  
Barbara Czepulkowski ◽  
Michael Schmitt ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Large Scale ◽  
Tumor Antigens ◽  
Cytotoxic T Lymphocyte ◽  
Dual Role ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Acute Myeloid

Leukemia associated antigens (LAAs) are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL) cloning, serological analysis of recombinant cDNA expression libraries (SEREX) and mass spectrometry (MS). In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs), serial analysis of gene expression (SAGE) and 2-dimensional gel electrophoresis (2-DE) have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML). It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel) and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.

Heterozygous deletion of the PU.1 locus in human AML

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 331-334 ◽  
Author(s):  
Nicola Bonadies ◽  
Thomas Pabst ◽  
Beatrice U. Mueller
Keyword(s):  
Acute Myeloid Leukemia ◽  
Loss Of Heterozygosity ◽  
Myeloid Leukemia ◽  
Regulatory Element ◽  
Nucleotide Polymorphisms ◽  
Heterozygous Deletion ◽  
Single Nucleotide ◽  
Upstream Regulatory Element ◽  
Myeloid Development ◽  
Acute Myeloid

Abstract The transcription factor PU.1 is essential for myeloid development. Targeted disruption of an upstream regulatory element (URE) decreases PU.1 expression by 80% and leads to acute myeloid leukemia (AML) in mice. Here, we sequenced the URE sequences of PU.1 in 120 AML patients. Four polymorphisms (single nucleotide polymorphisms [SNPs]) in the URE were observed, with homozygosity in all SNPs in 37 patients. Among them, we compared samples at diagnosis and remission, and one patient with cytogenetically normal acute myeloid leukemia M2 was identified with heterozygosity in 3 of the SNPs in the URE at remission. Loss of heterozygosity was further found in this patient at 2 polymorphic sites in the 5′ promoter region and in 2 intronic sites flanking exon 4, thus suggesting loss of heterozygosity covering at least 40 kb of the PU.1 locus. Consistently, PU.1 expression in this patient was markedly reduced. Our study suggests that heterozygous deletion of the PU.1 locus can be associated with human AML.

scholarly journals Modelling the Effects of MCM7 Variants, Somatic Mutations, and Clinical Features on Acute Myeloid Leukemia Susceptibility and Prognosis

2020 ◽  
Vol 9 (1) ◽  
pp. 158 ◽  
Author(s):  
Florin Tripon ◽  
Mihaela Iancu ◽  
Adrian Trifa ◽  
George Andrei Crauciuc ◽  
Alina Boglis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Variant Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mutation Status ◽  
Biological Features ◽  
Acute Myeloid

The main objective of the study was to evaluate the associations between MCM7 rs2070215, rs1527423, and rs1534309 single nucleotide polymorphisms (SNPs) and acute myeloid leukemia (AML) risk and prognosis. The secondary objectives were to assess if any relationships existed between the mentioned SNPs and FLT3, DNMT3A, NPM1 mutations with clinical outcomes and overall survival (OS) in AML patients. We investigated 281 AML cases and 405 healthy subjects. The results showed a significant association between a variant allele of rs2070215 (p = 0.007), CAT haplotype (p = 0.012), and AML susceptibility. No significant association was found between MCM7 variant genotypes and overall survival of AML patients (p > 0.05), while several associations between somatic mutations, clinical and biological features, and poor OS were noticed. Lactate dehydrogenase (LDH) level ≥ 600 IU/L had a significant effect on the hazard of death (p = 0.004, HR = 1.49, 95% CI: 1.13–1.95). Our study showed that the variant allele of rs2070215, in the allelic model, and CAT haplotype were associated with AML susceptibility. The investigated FLT3, DNMT3A, and NPM1 mutations were associated with the clinical and biological features and poor OS. LDH level ≥ 600 IU/L was associated with an increased hazard of death and this association remained significant when quantifying for effect modification by FLT3 mutation status.

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