Presentation Abstract
Abstract Number: 277
Presentation Title: "Genetic re-programming of the acute myeloid leukemia cell line HL-60".
Presentation Time: Sunday, Apr 03, 2011, 1:00 PM - 5:00 PM
Location: Exhibit Hall A4-C, Poster Section 11
Poster Section: 11
Poster Board Number: 19
"Genetic re-programming of the acute myeloid leukemia cell line HL-60".
Michael Roberts, David Bittner, Sarah Brnich, Bryan Conner, Carla Cox, Julia Filiberti, Michael Grant, Michael Mansuy, Jeffrey Forrester. Dickinson College, Carlisle, PA
Abstract Body:
HL-60 cells represent an established line of human acute myeloid leukemia cells that can be induced to differentiate along several distinct myeloid lineages. Phorbol esters activate a signaling network, which includes the protein kinase C (PKC) signaling pathway, causing the leukemia cells to differentiate into macrophage-like cells.
As the leukemia genetic program is converted to the macrophage program, the cells exit the cell cycle, undergo morphological changes, become adherent, display other macrophage properties, and ultimately initiate apoptosis.
This study provides a detailed DNA microarray analysis of the genetic network of the leukemia cell during first 24 hours post-induction of differentiation. Approximately 1,000 genes were identified that exhibit significant changes in mRNA levels from the leukemia expression profile.
A cluster analysis was performed to group these genes by their pattern of expression resulting in a collection of distinct expression profiles. Expression levels of selected genes within each cluster were validated by real time PCR. Among the most significant changes observed were dramatic increases in the expression of CCL chemokine family genes and a variety of transcription factor genes including members of the AP-1 and NF-kB families.
Expression level changes in genes involved in cell cycle progression (ex. MYC and p21) were also observed along with genes involved in the regulation of apoptosis (ex. BCL2A1, TNF, IER2 and OLR1). Functional analysis at the protein level using the electrophoretic mobility shift assay (EMSA), western blotting and immunofluorescence imaging will also be presented.
This study provides a comprehensive view of the re-programming events that occur in phorbol ester induced macrophage differentiation of HL-60 cells with regard to the inflammatory response, cell cycle exit, differentiation and initiation of apoptosis.
1. Frenster JH, and Hovsepian JA,
"Reprogramming
the human cancer cell nucleus".
1. Each cell retains all of its embryonic genes for a lifetime.
2. Controls for embryonic genes are often absent in adults.
3. Uncontrolled embryonic genes can replicate wildly.
4. Replicating genes participate in intra-cellular competition.
5. The basis for gene competition is selective transcription.
6. MicroRNAs can reprogram embryomic transcription.
7. Gene reprogramming can produce normal phenotypes.
8. Normal phenotypes can by-pass chromosomal lesions.
9. MicroRNA therapy may need to be permanent.
10. Transplantation of microRNAs could be preferred.
1. Pathways within cell genomes involve a flow of information.
2. Information can flow by direct contact or by third parties.
3. Direct contact within whole genomes is difficult to regulate.
4. DNA-DNA direct contects are influenced by agents.
5. Nuclear agents include hydrophilic ionic and hydrophobic conforming ligands.
6. Third parties within genomes involve RNAs and proteins.
7. RNAs and proteins are easy to regulate or reverse.
8. Information can be shared, lost, or transformed.
9. System information can be hidden during system isolation.
10. Local information can be permanently lost during system entropy.
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