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E-GEOD-66792 - Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages

Status
Released on 1 April 2015, last updated on 4 April 2015
Organism
Homo sapiens
Samples (15)
Array (1)
Protocols (7)
Description
BCR–ABL1+ precursor B-cell acute lymphoblastic leukemia (BCR– ABL1+ B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCR–ABL1+ B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBPα or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCR–ABL1+ B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14+ monocytes/ macrophages in BCR–ABL1+ B-ALL patient samples that possess the BCR–ABL1+ translocation and clonally recombined VDJ regions. We obtained the expression profiles of 5 human B-ALL samples using Afymmetrix U133A2 microarrays. Blasts were either analyzed without culture, or cultured in the presence of myeloid cytokines and sorted into CD14+ and CD19+ populations.
Experiment type
transcription profiling by array 
Contacts
Christopher Dove, J S McClellan
Citation
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-66792.idf.txt
Sample and data relationshipE-GEOD-66792.sdrf.txt
Raw data (1)E-GEOD-66792.raw.1.zip
Processed data (1)E-GEOD-66792.processed.1.zip
Array designA-GEOD-19883.adf.txt
Links