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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 25, 2019 |
| Title |
IL-12 abrogates calcineurin-dependent immune evasion during leukemia progression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Exploitation of the immune system has emerged as an important therapeutic strategy for acute lymphoblastic leukemia (ALL). However, the mechanisms of immune evasion during leukemia progression remain poorly understood. We sought to understand the role of calcineurin in ALL and observed that knocking-down calcineurin B (CnB) in leukemia cells dramatically prolonged survival in immune-competent but not immune-deficient recipients. Furthermore, immune-competent recipients were protected from challenge with leukemia if they were first immunized with CnB-deficient leukemia, suggesting robust adaptive immunity. In the bone marrow, recipients of CnB-deficient leukemia had expansion of T cell populations as compared to controls. Gene expression analyses of leukemia cells extracted from bone marrow identified Cn-dependent significant changes in the expression of immuno-regulatory genes. We confirmed increased secretion of IL-12 from CnB-deficient leukemia cells, sufficient to induce T cell activation ex vivo, an effect that was abolished when IL-12 was neutralized. Strikingly, recombinant IL-12 prolonged survival of mice challenged with highly aggressive B-ALL. Moreover, gene expression analyses from children with ALL demonstrate prolonged survival in those with higher expression of either IL-12A or IL-12B. These data suggest that leukemia cells are dependent upon calcineurin for immune evasion by restricting the regulation of pro-inflammatory genes, particularly IL-12.
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| Overall design |
8 samples total; 4 each of murine BCR-ABL1+/Arf null leukemia with a nonsilencing shRNA or shRNA directed against calcineurin B
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| Contributor(s) |
Rabe J, Porter C |
| Citation(s) |
31142509 |
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| Submission date |
Apr 24, 2019 |
| Last update date |
Jul 25, 2019 |
| Contact name |
Christopher Porter |
| E-mail(s) |
chris.porter@emory.edu
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| Organization name |
Emory University
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| Department |
Pediatrics
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| Street address |
1760 Haygood Drive
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA534497 |
| SRA |
SRP193770 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130272_RNA-Seq_shNS_v_shCn_-_all_-_counts_only.txt.gz |
631.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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