scholarly journals Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance

Oncotarget ◽  
2018 ◽  
Vol 9 (38) ◽  
pp. 24970-24979 ◽  
Author(s):  
Long Su ◽  
YeHui Tan ◽  
Hai Lin ◽  
XiaoLiang Liu ◽  
Li Yu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Next Generation ◽  
Mutational Spectrum ◽  
Cebpa Mutations ◽  
Generation Sequencing ◽  
Acute Myeloid

Evaluation of a 42-Gene Next-Generation Sequencing Panel for Detection of Acute Myeloid Leukemia Mutations for Clinical Use

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S114-S114
Author(s):  
Sun Hee Rosenthal ◽  
Anna Gerasimova ◽  
Charles Ma ◽  
Daniel Sugganth ◽  
Frederick Racke ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Clinical Diagnosis ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Analytical Sensitivity ◽  
Next Generation ◽  
Generation Sequencing ◽  
Acute Myeloid

Abstract Objectives Identification of genetic alterations by molecular and cytogenetic testing has an important role in the classification, risk stratification, and management of acute myeloid leukemia (AML). We evaluated a next-generation sequencing (NGS) panel that assesses IDH2, FLT3, NPM1, and TP3 and 38 other genes associated with diagnostic, prognostic, and/or therapeutic utility in AML, with a turnaround time of 8 to 14 days, using a DNA input of 50 ng. Methods In total, 110 patients, 65 males and 45 females, at a median age of 58 years (range: 2-68 years) with clinical diagnosis of AML were included in this study. Targeted regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. Sequence reads were analyzed using a bioinformatics pipeline that was developed in house. Analytical sensitivity of the assay is ~5% mutated alleles with 100% specificity. Results A total of 296 pathogenic mutations in 38 genes were detected in 95 of 110 samples (86%). On average, three mutations (range 1-10) were detected per positive sample. Variant frequency ranged from 3.0% to 96.1%. Most frequently mutated genes were TET2 (18.2%), FLT3 (18.2%), TP53 (17.3%), RUNX1 (15.5%), NPM1 (14.5%), ASXL1 (12.7%), NRAS (11.8%), and CEBPA (10.9%). In total, 166 of 296 (56%) mutations from 13 genes had prognostic significance, 42 of 296 (14%) mutations from three genes (CEBPA, NPM1, RUNX1) had diagnostic significance, and 40 of 296 (14%) mutations from three genes (IDH1, IDH2, FLT3) had therapeutic significance. Conclusion This focused 42-gene targeted panel identifies mutations of clinical significance in over 85% of patients with a clinical diagnosis of AML.

Mutational profiling of acute myeloid leukemia with normal cytogenetics in Brazilian patients: the value of next-generation sequencing for genomic classification

2017 ◽  
Vol 65 (8) ◽  
pp. 1155-1158 ◽  
Author(s):  
Thiago Rodrigo de Noronha ◽  
Miguel Mitne-Neto ◽  
Maria de Lourdes Chauffaille
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Regulation Of Gene Expression ◽  
Uniparental Disomy ◽  
Driver Mutations ◽  
Next Generation ◽  
Normal Cytogenetics ◽  
Generation Sequencing ◽  
Acute Myeloid

Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients’ risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes. Every patient presented at least one mutation:DNMT3Ain nine patients;IDH2in six;IDH1in three;NRASandNPM1in two; andTET2,ASXL1,PTPN11, andRUNX1in one patient. No mutations were found inFLT3,KIT,JAK2,CEBPA,GATA2,TP53,BRAF,CBL,KRAS,andWT1genes. Twelve patients (86%) had at least one mutation in genes related with DNA methylation (DNMT3A,IDH1,IDH2,andTET2), which is involved in regulation of gene expression and genomic stability. All patients could be reclassified based on genomic status and nine had their prognosis modified. In summary, NGS offers insights into the molecular pathogenesis and biology of cytogenetically normal AML in Brazilian patients, indicating that the prognosis could be further stratified by different mutation combinations. This study shows a different frequency of mutations in Brazilian population that should be confirmed.

scholarly journals Co-occurrence of immature T-lymphoblastic lymphoma and acute myeloid leukemia—microenvironment-dependent lineage differentiation derived from a common progenitor?

2021 ◽  
Author(s):  
Edit Porpaczy ◽  
Wolfgang R. Sperr ◽  
Renate Thalhammer ◽  
Gerlinde Mitterbauer-Hohendanner ◽  
Leonhard Müllauer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Genetic Alterations ◽  
Lymphoblastic Lymphoma ◽  
Simultaneous Occurrence ◽  
Next Generation ◽  
T Lymphoblastic Lymphoma ◽  
Generation Sequencing ◽  
Acute Myeloid

AbstractMixed phenotype acute leukemia (MPAL) is an uncommon disease characterized by currently only limited knowledge concerning biology, clinical presentation, and treatment outcome. We here describe a most unusual case of simultaneous occurrence of T-lymphoblastic lymphoma in cervical and mediastinal lymph nodes and acute myeloid leukemia in the bone marrow (BM) successfully treated with allogeneic stem cell transplantation (SCT). Although the blasts in both locations showed additional aberrant expression of other lineage markers (even B-cell markers), diagnostic criteria of MPAL were not fulfilled either in the LN or in the BM. We performed next generation sequencing (NGS) with the objective to look for common genetic aberrations in both tissues. Histology, immunohistochemistry, flow cytometry, AML-associated genetic alterations (FLT3, NPM1, KIT D816V, CEPBA), and clonal T-cell receptor β and γ gene rearrangements were performed according to routine diagnostic workflows. Next generation sequencing and Sanger sequencing were additionally performed in BM and LN. Somatic mutation in the EZH2 gene (p.(Arg684Cys)) was detected in the BM by NGS, and the same mutation was found in the LN. Since an identical genetic aberration (EZH2 mutation) was detected in both locations, a common progenitor with regional dependent differentiation may be involved.

Impact of intra-tumoral heterogeneity detected by next-generation sequencing on acute myeloid leukemia survival

2020 ◽  
Vol 61 (13) ◽  
pp. 3269-3271
Author(s):  
Wade L. Schulz ◽  
Henry M. Rinder ◽  
Thomas J. S. Durant ◽  
Christopher A. Tormey ◽  
Richard Torres ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Next Generation ◽  
Generation Sequencing ◽  
Acute Myeloid

Next-generation sequencing panel in de novo acute myeloid leukemia

2019 ◽  
Vol 85 ◽  
pp. S69-S70
Author(s):  
A. Bolaman ◽  
İ. Erdoğdu ◽  
A. Turgutkaya ◽  
C. Selim ◽  
A. Eroglu Kucukerdiler ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Next Generation ◽  
Generation Sequencing ◽  
Acute Myeloid
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