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| Status |
Public on Dec 27, 2008 |
| Title |
Gene expression profiling of LMO2 associated T cell lymphoblastic leukemia induced by insertional mutagenesis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Aberrant co-expression of LMO2 and TAL1 is regularly found in T cell acute lymphoblastic leukemia (T-ALL). Here we describe a xenotransplant model for primary T-ALL cells derived from a patient who developed LMO2/TAL1 associated T-ALL after gene therapy for X-SCID (gamma c deficiency) due to insertional activation and a SIL-TAL1 fusion as an additional independent event. We identified a protein complex containing LMO2, TAL1 and E47 in the patient’s T-ALL cells. This complex functions as a transcription regulation complex in undifferentiated hematopoietic cells. However, its role in T-ALL is not fully understood. By comparative gene expression profiling we identified retinaldehyde dehydrogenase (RALDH2) as one of the genes which was highly up regulated in the primary T-ALL cells; the gene product was N-terminally truncated (RALDH2-T), but enzymatically active. To investigate the interference of LMO2 in RALDH2-T expression as well as the role of RALDH2-T in T-ALL development, LMO1 (analogue of LMO2) was down regulated by RNA interference in the T-ALL cell line Jurkat which led to a decrease of RALDH2-T expression and cell viability, indicating that positive regulation of RALDH2-T through an LMO1 or 2 containing transcription regulation complex might be essential for maintaining the T-ALL phenotype.
Keywords: Primary human T-ALL cells and CD8 cells of normal donors
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| Overall design |
To decipher target genes of an LMO2 associated transcription regulation complex in primary T cell acute lymphoblastic leukemia cells and its contribution to the onset of malignancy.
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| Contributor(s) |
Layh-Schmitt G, Jansen M, Rosenstiel A, Wang W, Koch S, Wittlinger C, Klanke C, Bailey J, McCaffery P, von Kalle C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jan 30, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Gerlinde Layh-Schmitt |
| E-mail(s) |
gerlinde.layh-schmitt@cchmc.org
|
| Organization name |
Cincinnati Children's Hospital Research Foundation
|
| Department |
Experimental Hematology
|
| Lab |
Molecular and Gene Therapy
|
| Street address |
3333 Burnet Ave
|
| 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 (6)
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| GSM159403 |
Patient 5 T-ALL cells propagated in NOD/SCID mice and harvested from bone marrow; first of two replicates. |
| GSM159404 |
Patient 5 T-ALL cells propagated in NOD/SCID mice and harvested from bone marrow; second of two replicates. |
| GSM159405 |
CD8 cells isolated from mixed normal donors; first of two replicates. |
| GSM159406 |
CD8 cells isolated from mixed normal donors; second of two replicates. |
| GSM159407 |
Primary T-ALL cells isolated from patient 5; first of two replicates. |
| GSM159408 |
Primary T-ALL cells isolated from patient 5; second of two replicates. |
|
| Relations |
| BioProject |
PRJNA98137 |
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