Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement
Infant acute lymphoblastic leukemia (ALL) with the mixed lineage leukemia (MLL) gene rearrangement (MLL-R) is considered a distinct leukemia from childhood or non-MLL-R infant ALL. To detect key genes and elucidate the molecular mechanisms of MLL-R infant ALL, microarray expression data were downloa...
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PeerJ Inc.
2019-08-01
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| Online Access: | https://peerj.com/articles/7628.pdf |
| _version_ | 1797419357425369088 |
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| author | Hao Zhang Juan Cheng Zijian Li Yaming Xi |
| author_facet | Hao Zhang Juan Cheng Zijian Li Yaming Xi |
| author_sort | Hao Zhang |
| collection | DOAJ |
| description | Infant acute lymphoblastic leukemia (ALL) with the mixed lineage leukemia (MLL) gene rearrangement (MLL-R) is considered a distinct leukemia from childhood or non-MLL-R infant ALL. To detect key genes and elucidate the molecular mechanisms of MLL-R infant ALL, microarray expression data were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between MLL-R and non-MLL-R infant ALL were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Then, we constructed a protein-protein interaction (PPI) network and identified the hub genes. Finally, drug-gene interactions were mined. A total of 139 cases of MLL-R infant ALL including 77 (55.4%) fusions with AF4, 38 (27.3%) with ENL, 14 (10.1%) with AF9, and 10 (7.2%) other gene fusions were characterized. A total of 236 up-regulated and 84 down-regulated DEGs were identified. The up-regulated DEGs were mainly involved in homophilic cell adhesion, negative regulation of apoptotic process and cellular response to drug GO terms, while down-regulated DEGs were mainly enriched in extracellular matrix organization, protein kinase C signaling and neuron projection extension GO terms. The up-regulated DEGs were enriched in seven KEGG pathways, mainly involving transcriptional regulation and signaling pathways, and down-regulated DEGs were involved in three main KEGG pathways including Alzheimer’s disease, TGF-beta signaling pathway, and hematopoietic cell lineage. The PPI network included 297 nodes and 410 edges, with MYC, ALB, CD44, PTPRC and TNF identified as hub genes. Twenty-three drug-gene interactions including four up-regulated hub genes and 24 drugs were constructed by Drug Gene Interaction database (DGIdb). In conclusion, MYC, ALB, CD44, PTPRC and TNF may be potential bio-markers for the diagnosis and therapy of MLL-R infant ALL. |
| first_indexed | 2024-03-09T06:47:07Z |
| format | Article |
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| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:47:07Z |
| publishDate | 2019-08-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-4ed136c376514e168446f248dd96413d2023-12-03T10:34:13ZengPeerJ Inc.PeerJ2167-83592019-08-017e762810.7717/peerj.7628Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangementHao Zhang0Juan Cheng1Zijian Li2Yaming Xi3Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaInfant acute lymphoblastic leukemia (ALL) with the mixed lineage leukemia (MLL) gene rearrangement (MLL-R) is considered a distinct leukemia from childhood or non-MLL-R infant ALL. To detect key genes and elucidate the molecular mechanisms of MLL-R infant ALL, microarray expression data were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between MLL-R and non-MLL-R infant ALL were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Then, we constructed a protein-protein interaction (PPI) network and identified the hub genes. Finally, drug-gene interactions were mined. A total of 139 cases of MLL-R infant ALL including 77 (55.4%) fusions with AF4, 38 (27.3%) with ENL, 14 (10.1%) with AF9, and 10 (7.2%) other gene fusions were characterized. A total of 236 up-regulated and 84 down-regulated DEGs were identified. The up-regulated DEGs were mainly involved in homophilic cell adhesion, negative regulation of apoptotic process and cellular response to drug GO terms, while down-regulated DEGs were mainly enriched in extracellular matrix organization, protein kinase C signaling and neuron projection extension GO terms. The up-regulated DEGs were enriched in seven KEGG pathways, mainly involving transcriptional regulation and signaling pathways, and down-regulated DEGs were involved in three main KEGG pathways including Alzheimer’s disease, TGF-beta signaling pathway, and hematopoietic cell lineage. The PPI network included 297 nodes and 410 edges, with MYC, ALB, CD44, PTPRC and TNF identified as hub genes. Twenty-three drug-gene interactions including four up-regulated hub genes and 24 drugs were constructed by Drug Gene Interaction database (DGIdb). In conclusion, MYC, ALB, CD44, PTPRC and TNF may be potential bio-markers for the diagnosis and therapy of MLL-R infant ALL.https://peerj.com/articles/7628.pdfAcute lymphoblastic leukemiaInfantMixed-lineage leukemiaGene expression profilesDifferentially expressed genes |
| spellingShingle | Hao Zhang Juan Cheng Zijian Li Yaming Xi Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement PeerJ Acute lymphoblastic leukemia Infant Mixed-lineage leukemia Gene expression profiles Differentially expressed genes |
| title | Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement |
| title_full | Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement |
| title_fullStr | Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement |
| title_full_unstemmed | Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement |
| title_short | Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement |
| title_sort | identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with mll gene rearrangement |
| topic | Acute lymphoblastic leukemia Infant Mixed-lineage leukemia Gene expression profiles Differentially expressed genes |
| url | https://peerj.com/articles/7628.pdf |
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