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Title: RNA-sequencing of human B cells to investigate chronic lymphocytic leukemia mutations observed in hematopoietic multipotent progenitor fractions      
dateReleased:
01-12-2015
description:
Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in western countries, is a clonal accumulation of mature B-lymphocytes and its natural history is yet unclear. By using sequencing and cellular biology approaches on a cohort of CLL patient samples, we show here that acquired CLL mutations are observed in hematopoietic multipotent progenitor fractions in the majority of patients. These early CLL mutations include recurrent inactivating mutations in NFKBIE (10.7%) and missense mutations in BRAF (3.6%) and EGR2 (8.3%). Functional analyses demonstrated that BRAF-G469R affects lymphoid differentiation and transforms the T-cell lineage in vivo. In addition, the EGR2 recurrent mutations were associated with transcriptional activation of EGR2 target genes in patients and cell cycle abnormality in cellular model. Our findings indicate that CLL may develop from an initial infra-clinic, pre-leukemic phase affecting immature hematopoietic cells. We perform RNA-seq experiments on three EGR2-E356K samples, one EGR2-H384N sample and seven EGR2 wildtype patients. The RNA was extracted from B cells. The cDNA libraries were prepared using the ScriptSeq Complete Kit (Epicentre) and we performed paired-end sequencing (100 bp) using HiSeq2000 sequencing instruments.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-1776
refinement:
raw
keywords:
functional genomics
dateModified:
07-20-2015
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1776/E-MTAB-1776.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1776/E-MTAB-1776.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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