E-GEOD-11889 - Transcription profiling of human CD34+ subsets in chronic phase CML and healthy individuals

Status
Submitted on 26 June 2008, released on 13 January 2009, last updated on 1 May 2014
Organism
Homo sapiens
Samples (47)
Array (1)
Protocols (4)
Description
A characteristic of chronic phase CML is accumulation of mature cells in the peripheral blood. It has not been determined if this expansion is explained by the CD34+ cell subset composition. We conducted flowcytometry-based cell sorting to assess the CD34+ subset composition and to retrieve the respective cells. We found a significant increase in the proportion of MEP and a decrease of HSC and GMP in patients with chronic phase CML compared to their healthy counterparts. The absolute number of HSC was similar, whereas CMP, GMP and MEP were expanded 2.8- to 7.7-fold. Gene expression analysis of CD34+ cell subsets showed, that in contrast to the normal developmental hierachy, CML HSC have a transcriptional profile which is similar to CML progenitor subsets and healthy CMP. HSC in healthy individuals show greater distance to their more mature progeny within the developmental hierarchy. As the differences between CML and healthy controls were minor at the progenitor level, we focused on the further characterization of CML HSC. 614 genes were differentially expressed, including downregulation of genes involved in adhesion and migration, regulation of the stem cell pool, and differentiation. We also found abrogation of nuclear receptors NR4A1 and NR4A3, and decreased expression of c-Jun and JunB. Re-expression of c-Jun and JunB in CD34+ cells from CML patients was achieved by co-transfection of NR4A1 and NR4A3. Moreover, we functionally corroborated a decreased adhesion capacity of the CML HSC. Taken together, these findings help to explain the hematological phenotype of CML patients in chronic phase. Experiment Overall Design: CD34+ subsets of 6 patients with chronic phase CML and 5 healthy volunteers were analysed by means of gene expression profiling with the Affymetrix HU-133A 2.0 array
Experiment types
transcription profiling by array, unknown experiment type
Contact
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-11889.idf.txt
Sample and data relationshipE-GEOD-11889.sdrf.txt
Raw data (1)E-GEOD-11889.raw.1.zip
Processed data (1)E-GEOD-11889.processed.1.zip
Experiment designE-GEOD-11889.biosamples.png, E-GEOD-11889.biosamples.svg
Array designA-AFFY-37.adf.txt
R ExpressionSetE-GEOD-11889.eSet.r
Links