The modular network structure of the mutational landscape of Acute Myeloid Leukemia Article Swipe
Mariam Ibáñez
,
José Carbonell‐Caballero
,
Esperanza Such
,
Luz García‐Alonso
,
Alessandro Liquori
,
Maria López‐Pavía
,
Marta Llop
,
Carmen Alonso
,
Eva Barragán
,
Inés Gómez‐Seguí
,
Alexander Neef
,
David Hervás
,
Pau Montesinos
,
Guillermo Sanz
,
Miguel Á. Sanz
,
Joaquı́n Dopazo
,
José Cervera
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0202926
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0202926
Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.
Related Topics
Concepts
CEBPA
NPM1
Myeloid leukemia
Biology
Exome sequencing
Genetic heterogeneity
Leukemia
Genetics
Exome
Gene
Karyotype
Cancer research
Mutation
Phenotype
Chromosome
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0202926
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202926&type=printable
- OA Status
- gold
- Cited By
- 9
- References
- 65
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2896973056
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2896973056Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pone.0202926Digital Object Identifier
- Title
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The modular network structure of the mutational landscape of Acute Myeloid LeukemiaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
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2018-10-10Full publication date if available
- Authors
-
Mariam Ibáñez, José Carbonell‐Caballero, Esperanza Such, Luz García‐Alonso, Alessandro Liquori, Maria López‐Pavía, Marta Llop, Carmen Alonso, Eva Barragán, Inés Gómez‐Seguí, Alexander Neef, David Hervás, Pau Montesinos, Guillermo Sanz, Miguel Á. Sanz, Joaquı́n Dopazo, José CerveraList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0202926Publisher landing page
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202926&type=printableDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202926&type=printableDirect OA link when available
- Concepts
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CEBPA, NPM1, Myeloid leukemia, Biology, Exome sequencing, Genetic heterogeneity, Leukemia, Genetics, Exome, Gene, Karyotype, Cancer research, Mutation, Phenotype, ChromosomeTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 1, 2023: 1, 2022: 1, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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65Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.and | 89, 157 |
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| abstract_inverted_index.with | 6, 56, 86, 94, 99, 169 |
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| abstract_inverted_index.(NK), | 32 |
| abstract_inverted_index.(WES) | 64 |
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| abstract_inverted_index.After | 145 |
| abstract_inverted_index.CEBPA | 78 |
| abstract_inverted_index.NPM1, | 77 |
| abstract_inverted_index.Novel | 96 |
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| abstract_inverted_index.model | 156 |
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| abstract_inverted_index.performed | 61 |
| abstract_inverted_index.potential | 87 |
| abstract_inverted_index.relevance | 91 |
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| abstract_inverted_index.described, | 102 |
| abstract_inverted_index.enrichment | 148 |
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| abstract_inverted_index.prognosis. | 38 |
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| abstract_inverted_index.seed-genes | 162 |
| abstract_inverted_index.sequencing | 63 |
| abstract_inverted_index.sequential | 8 |
| abstract_inverted_index.alterations | 18 |
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| abstract_inverted_index.deregulated | 196 |
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| abstract_inverted_index.heterogeneous | 37 |
| abstract_inverted_index.implications. | 59 |
| abstract_inverted_index.heterogeneity, | 43 |
| abstract_inverted_index.leukemogenesis | 166 |
| abstract_inverted_index.candidate-genes, | 97 |
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| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5008521472, https://openalex.org/A5041081942, https://openalex.org/A5068275399, https://openalex.org/A5066552050, https://openalex.org/A5024908600, https://openalex.org/A5003682435, https://openalex.org/A5011739132, https://openalex.org/A5005116367, https://openalex.org/A5088243670, https://openalex.org/A5030067333, https://openalex.org/A5043157565, https://openalex.org/A5066796940, https://openalex.org/A5017341923, https://openalex.org/A5023063042, https://openalex.org/A5002126134, https://openalex.org/A5074140420, https://openalex.org/A5052934298 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 17 |
| corresponding_institution_ids | https://openalex.org/I1303153112, https://openalex.org/I2800982320, https://openalex.org/I3019010403, https://openalex.org/I4210086910, https://openalex.org/I4210087039, https://openalex.org/I4210107147, https://openalex.org/I4210111366, https://openalex.org/I4210119293, https://openalex.org/I4210158561, https://openalex.org/I4210166036 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7200000286102295 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.74405094 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |