Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia withMLLgene rearrangement

Abstract

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 ofMLL-R infant ALL, microarray expression data were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) betweenMLL-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 ofMLL-R infant ALL including 77 (55.4%) fusions withAF4, 38 (27.3%) withENL, 14 (10.1%) withAF9, 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, withMYC,ALB,CD44,PTPRCandTNFidentified 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,PTPRCandTNFmay be potential bio-markers for the diagnosis and therapy ofMLL-R infant ALL.

Integrated Transcriptome Profiling Identifies Prognostic Hub Genes as Therapeutic Targets of Glioblastoma: Evidenced by Bioinformatics Analysis

“…Drugs were identified through the Drug Gene Interaction Database (DGIdbv3.0.2;) for hub genes, which can serve as promising targets for GBM. , DGIdb is a user-friendly drug–gene interaction and the druggable genome data mining database, which mined the data from over 30 trusted sources such as ChEMBL, DrugBank, Ensembl, NCBI Entrez, PharmGKB, PubChem, clinical trial databases, and the literature in NCBI PubMed . Drugs were selected, which are supported by more than one database or have PUBMED references.…”

The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia

“…By the end of gestation, it is probable that pre-malignant cells have colonized the BM. There is evidence that multiple first-hit mutations can change B cell adhesion/migration properties; for example, ETV6::RUNX1 is associated with a cell-intrinsic defect in CXCR4-CXCL12 signaling ( 35 ) and KMT2A -mutated BCP-ALL up-regulates protocadherin genes ( 36 ). An area of active interest is whether pre-leukemic cells can modify the BM niche prior to transformation; given the changes seen at the time of diagnosis (see below) this seems likely and novel experimental co-culture techniques will help in delineating these interactions.…”

The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia

“…Moreover, gene expression studies that compared KMT2A -rearranged with non- KMT2A -rearranged infant ALL cases identified in KMT2A -rearranged samples the up-regulation of genes involved in homophilic cell adhesion (in particular protocadherin ( PCDH ) γ subfamily of genes). It has been assumed that the overexpression of these genes may cause different cell migration and invasion properties of KMT2A -rearranged cells [ 39 ].…”