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A B-cell developmental gene regulatory network is activated in infant AML
- Source :
- PLoS ONE, Vol 16, Iss 11, p e0259197 (2021), PLoS ONE, PLoS ONE, Vol 16, Iss 11 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- Infant Acute Myeloid Leukemia (AML) is a poorly-addressed, heterogeneous malignancy distinguished by surprisingly few mutations per patient but accompanied by myriad age-specific translocations. These characteristics make treatment of infant AML challenging. While infant AML is a relatively rare disease, it has enormous impact on families, and in terms of life-years-lost and life limiting morbidities. To better understand the mechanisms that drive infant AML, we performed integrative analyses of genome-wide mRNA, miRNA, and DNA-methylation data in diagnosis-stage patient samples. Here, we report the activation of an onco-fetal B-cell developmental gene regulatory network in infant AML. AML in infants is genomically distinct from AML in older children/adults in that it has more structural genomic aberrations and fewer mutations. Differential expression analysis of ~1500 pediatric AML samples revealed a large number of infant-specific genes, many of which are associated with B cell development and function. 18 of these genes form a well-studied B-cell gene regulatory network that includes the epigenetic regulators BRD4 and POU2AF1, and their onco-fetal targets LIN28B and IGF2BP3. All four genes are hypo-methylated in infant AML. Moreover, micro-RNA Let7a-2 is expressed in a mutually exclusive manner with its target and regulator LIN28B. These findings suggest infant AML may respond to bromodomain inhibitors and immune therapies targeting CD19, CD20, CD22, and CD79A.
- Subjects :
- B Cells
Gene regulatory network
Cell Cycle Proteins
Biochemistry
Pediatrics
Hematologic Cancers and Related Disorders
Families
White Blood Cells
Animal Cells
hemic and lymphatic diseases
Medicine and Health Sciences
Gene Regulatory Networks
Children
B-Lymphocytes
Multidisciplinary
Leukemia
DNA methylation
biology
Myeloid leukemia
RNA-Binding Proteins
Hematology
Genomics
Myeloid Leukemia
Chromatin
Up-Regulation
Nucleic acids
Leukemia, Myeloid, Acute
Oncology
Medicine
Epigenetics
Cellular Types
DNA modification
Infants
Chromatin modification
Research Article
Chromosome biology
Acute Myeloid Leukemia
BRD4
Immune Cells
Science
Immunology
CD19
microRNA
Genetics
Humans
RNA, Messenger
Antibody-Producing Cells
Non-coding RNA
Gene
Natural antisense transcripts
Blood Cells
Infant
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
DNA
Gene regulation
MicroRNAs
Age Groups
People and Places
biology.protein
Cancer research
Trans-Activators
RNA
Population Groupings
Gene expression
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 16
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3022a5655740e23fc0b7dcf84b1d6af0