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3D genome alterations associated with dysregulated HOXA13 expression in high-risk T-lineage acute lymphoblastic leukemia
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- 3D genome alternations can dysregulate gene expression by rewiring enhancer-promoter interactions and lead to diseases. We report integrated analyses of 3D genome alterations and differential gene expressions in 18 newly diagnosed T-lineage acute lymphoblastic leukemia (T-ALL) patients and 4 healthy controls. 3D genome organizations at the levels of compartment, topologically associated domains and loop could hierarchically classify different subtypes of T-ALL according to T cell differentiation trajectory, similar to gene expressions-based classification. Thirty-four previously unrecognized translocations and 44 translocation-mediated neo-loops are mapped by Hi-C analysis. We find that neo-loops formed in the non-coding region of the genome could potentially regulate ectopic expressions of TLX3, TAL2 and HOXA transcription factors via enhancer hijacking. Importantly, both translocation-mediated neo-loops and NUP98-related fusions are associated with HOXA13 ectopic expressions. Patients with HOXA11-A13 expressions, but not other genes in the HOXA cluster, have immature immunophenotype and poor outcomes. Here, we highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.<br />The non-coding genome of T-ALL has not been extensively studied. Here, the authors conduct RNA-seq, ATAC-seq and Hi-C seq analyses and find that T-ALL associated neo-loops may regulate key transcription factors including HOXA13; the aberrant expression of which is associated with poor prognosis.
- Subjects :
- 0301 basic medicine
T-Lymphocytes
genetic processes
Molecular Conformation
General Physics and Astronomy
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Genome
Translocation, Genetic
Histones
0302 clinical medicine
Cancer genomics
Basic Helix-Loop-Helix Transcription Factors
Leukemia-Lymphoma, Adult T-Cell
Child
Regulation of gene expression
Genetics
Multidisciplinary
Gene Expression Regulation, Leukemic
Acetylation
Prognosis
Neoplasm Proteins
Enhancer Elements, Genetic
030220 oncology & carcinogenesis
Disease Progression
Chromatin Immunoprecipitation Sequencing
HOXA13
Science
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Chromosomes
Immunophenotyping
03 medical and health sciences
Young Adult
Cancer epigenetics
Cell Line, Tumor
Humans
natural sciences
Cell Lineage
Enhancer
Transcription factor
Gene
Homeodomain Proteins
Acute lymphocytic leukaemia
Gene Expression Profiling
General Chemistry
Hematopoiesis
Gene expression profiling
Nuclear Pore Complex Proteins
030104 developmental biology
Gene Ontology
TAL2
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....69f50bf116c439bbf4688221cc3b3079