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| Status |
Public on May 01, 2008 |
| Title |
Leukemia fusion-gene transduced human cord blood cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
MLL-AF9 expression in normal human umbilical cord blood CD34+ cells leads to long-term proliferation of a myeloid progenitor cell with leukemogenic potential. Expression of a Core Binding Factor leukemia fusion (AML1-ETO or CBFbeta-SMMHC) in human CD34+ cells results in self-renewal of primitive progenitor cells with multilineage potential and stem cell ability, but these cells do not induce leukemia in immunodeficient mice. This comparative microarray study was initiated to determine how faithful these cell cultures are to the transcriptome of patient samples expressing each of these different fusion proteins, and to analyze the signaling pathways that are unique to CBF cultures and MLL-fusion cultures, with the hope of determining why the MLL-fusion cells are leukemogenic while the CBF cells are not.
Keywords: Disease state analysis; comparison of leukemia fusion gene expression in normal human hematopoietic progenitor cells
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| Overall design |
We have established a culture system whereby we retrovirally transduce human CD34+ cells, obtained from cord blood, with the leukemia fusion genes MLL-AF9 (MA9), AML1-ETO (AE) or CBFbetaMYH11 (CM). Cells expressing each of these fusion proteins are able to proliferate long-term in vitro in a cytokine dependent manner. These cultures resemble somewhat the blast samples from patients that contain these different fusion proteins, in that MA9 cells are predominantly monocytic (M5-like), AE cells have a large population of primitive CD34+ cells with continued abnormal differentiation (M2-like) and CM cells also contain a population of primitive CD34+ cells with continued abnormal differentiation but also have a significant population of abnormal eosinophils (M4Eo). We grow these cells in the presence of fetal bovine serum (FBS), and also grow them in serum-free conditions using the BIT supplement from Stem Cell Technologies. For the current experiments we used cell cultures that had been proliferating in vitro for 8-12 weeks, in either serum-free conditions or with FBS. Replicate samples were included in some instances, and the same clonal cultures that were grown under either BIT or FBS were also included.
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| Contributor(s) |
Wei J, Wunderlich M, Jansen M, Fox C, Mulloy J, DiMartino J, Krejci O, Gu Y, Wilhelm J, Alvarez S, Cigudosa J |
| Citation(s) |
18538732 |
| Submission date |
Feb 12, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
James Mulloy |
| E-mail(s) |
james.mulloy@cchmc.org
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| Phone |
(513) 636-1844
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| Fax |
513-636-3768
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| URL |
http://www.cincinnatichildrens.org/research/div/exp-hematology/labs/genotox/mulloy/
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| Organization name |
Cincinnati Children's Hospital Research Foundation
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| Department |
Experimental Hematology
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| Lab |
ML7013
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| Street address |
3333 Burnet Ave
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (18)
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| GSM161803 |
AML1-ETO expressing cord blood cell, clone 18, grown serum-free, replicate 1 |
| GSM161804 |
AML1-ETO expressing cord blood cell, clone 18, grown serum-free, replicate 2 |
| GSM161805 |
AML1-ETO expressing cord blood cell, clone 17, grown serum-free, replicate 1 |
| GSM161806 |
AML1-ETO expressing cord blood cell, clone 17, grown serum-free, replicate 2 |
| GSM161807 |
AML1-ETO expressing cord blood cell, clone 4, grown serum-free |
| GSM161808 |
MLL-AF9 expressing cord blood cell, clone 4, grown serum-free |
| GSM161809 |
CBFbeta-MYH11 expressing cord blood cell, clone 2.2, grown serum-free, replicate 1 |
| GSM161810 |
CBFbeta-MYH11 expressing cord blood cell, clone 2.2, grown serum-free, replicate 2 |
| GSM161811 |
CBFbeta-MYH11 expressing cord blood cell, clone 6, grown serum-free |
| GSM161812 |
AML1-ETO expressing cord blood cell, clone 18, grown with serum, replicate 2 |
| GSM161813 |
MLL-AF9 expressing cord blood cell, clone 1, grown with serum |
| GSM161814 |
MLL-AF9 expressing cord blood cell, clone 3, grown with serum |
| GSM161815 |
MLL-AF9 expressing cord blood cell, clone 4, grown with serum |
| GSM161816 |
MLL-AF9 expressing cord blood cell, clone 5, grown with serum |
| GSM161817 |
MLL-AF9 expressing cord blood cell, clone 1, grown serum-free, replicate 1 |
| GSM161818 |
MLL-AF9 expressing cord blood cell, clone 1, grown serum-free, replicate 2 |
| GSM161819 |
MLL-AF9 expressing cord blood cell, clone 3, grown serum-free, replicate 1 |
| GSM161820 |
MLL-AF9 expressing cord blood cell, clone 3, grown serum-free, replicate 2 |
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| Relations |
| BioProject |
PRJNA98353 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE7011_RAW.tar |
89.6 Mb |
(http)(custom) |
TAR (of CEL) |
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