|
| Status |
Public on Feb 01, 2016 |
| Title |
Truncating erythropoietin receptor rearrangements in acute lymphoblastic leukemia |
| Organism |
Mus musculus |
| Experiment type |
Genome variation profiling by genome tiling array
|
| Summary |
Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia
chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This
resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic
option in high-risk ALL.
|
| |
|
| Overall design |
Mice expressing truncated EPOR were analyzed
|
| |
|
| Contributor(s) |
Iacobucci I, Li Y, Mullighan CG |
| Citation(s) |
26859458 |
| |
| Submission date |
Dec 16, 2015 |
| Last update date |
May 02, 2016 |
| Contact name |
Charles G Mullighan |
| E-mail(s) |
charles.mullighan@stjude.org
|
| Phone |
1-901-595-3387
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Pathology
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10448 |
Agilent-027414 SurePrint G3 Mouse CGH Microarray 1x1M |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA306132 |
