|
| Status |
Public on Jan 29, 2019 |
| Title |
The age of the hematopoietic microenvironment specifies lineage in MLL-rearranged leukemia [Ccl5] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The defining characteristics of leukemia, such as lineage and genetics, are associated with a typical age of onset. Understanding mechanisms of leukemia age specificity could improve disease models to develop new therapies. We used heterochronic transplantation of murine leukemia driven by MLL-AF9 to investigate the relative contribution of the age of the cell-of-origin or the hematopoietic microenvironment to the lineage fate of leukemia initiating cells (LICs). We show that the neonatal hematopoietic niche supports the development of infant-like mixed lineage B-cell/myeloid leukemia, while a mature niche promotes adult-like pure acute myeloid leukemia (AML) from identical cells of origin. We attribute this to inhibition of B-lymphoid fate in multipotent progenitor-like LICs by Ccl5 from adult bone marrow (BM) stroma, and implicate glycogen synthase kinase-3 (GSK-3) signaling in the myeloid fate specification in mouse and human MLL-driven leukemia. These findings connect maturation and aging of the hematopoietic system to leukemia age specificity.
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| |
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| Overall design |
Primary neonatal murine leukemia treated with ccl5 or under control conditions
|
| |
|
| Contributor(s) |
Rowe RG, da Rocha EL |
| Citation(s) |
30728174 |
| |
| Submission date |
Oct 17, 2017 |
| Last update date |
Oct 16, 2019 |
| Contact name |
Edroaldo Lummertz da Rocha |
| E-mail(s) |
edroaldo@gmail.com
|
| Organization name |
Boston Children's Hospital
|
| Department |
Hematology/Oncology
|
| Lab |
Daley Lab
|
| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE105087 |
The age of the hematopoietic microenvironment specifies lineage in MLL-rearranged leukemia |
|
| Relations |
| BioProject |
PRJNA414617 |
| SRA |
SRP120162 |
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