|
| Status |
Public on Dec 01, 2018 |
| Title |
ASXL2 is recurrently mutated in t(8;21) AML and regulates hematopoietic development [RNA_Seq_Asxl2_mutant] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Chromosomal translocation t(8;21) (q22;q22) leading to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is a cytogenetic abnormality observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed targeted and whole exome sequencing of newly-diagnosed and relapsed AML samples. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal and malignant hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid cell expansion, splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in transplantation models. A parallel analysis of young and >1-year old Asxl2-deficient mice revealed age-dependent changes in the hematopoietic compartment leading to perturbations affecting not only myeloid and erythroid differentiation but also maturation of lymphoid cells. Our studies also suggest that expression of truncated ASXL2 protein confers proliferative advantage to mouse myeloid progenitors. Overall, these findings establish a critical role of ASXL2 in maintaining steady state hematopoiesis and provide insights into how its loss/mutation primes leukemic growth of myeloid cells.
|
| |
|
| Overall design |
Gene expression analysis of bone marrow derived Lin- Kit+ cells expressing either mutant or full-length ASXL2
|
| |
|
| Contributor(s) |
Madan V, Han L, Koeffler HP |
| Citation(s) |
30093396 |
| |
| Submission date |
Nov 13, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Phillip H Koeffler |
| E-mail(s) |
phillip_koeffler@nuhs.edu.sg
|
| Organization name |
Cancer Science Institute
|
| Lab |
H. Phillip Koeffler's lab
|
| Street address |
14 Medical Drive
|
| City |
Singapore |
| ZIP/Postal code |
117599 |
| Country |
Singapore |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (10)
|
|
| This SubSeries is part of SuperSeries: |
| GSE106798 |
ASXL2 is recurrently mutated in t(8;21) AML and regulates hematopoietic development |
|
| Relations |
| BioProject |
PRJNA418089 |
| SRA |
SRP124823 |
Less...
More...