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| Status |
Public on Feb 24, 2020 |
| Title |
Combined mutation of C/EBPa and GATA-2 induce bi-lineage acute erythroid leukemia through transformation of a neomorphic neutrophil-erythroid progenitor [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Acute erythroid leukemia (AEL) most commonly involves transformation of both the myeloid and erythroid lineages. However, the mutations that cause AEL and the nature of the transformed cell that sustains the bi-lineage leukemia phenotype remain unknown. We here show that combined bi-alleCD45.2+LKFcgRII/III+CD55- C/EBPa and GATA-2 zinc finger 1 (ZnF1) mutations are sufficient to induce bi-lineage AEL, and that the leukemia-initiating cell has a Lin–Sca-1–c-Kit+CD150–FcyRII/III+ surface phenotype, consistent with a committed myeloid progenitor. However, we find that in the presence of bi-alleCD45.2+LKFcgRII/III+CD55- C/EBPa mutation this cell population acquires ectopic erythroid gene expression and lineage potential, leading to the formation of neomorphic neutrophil-erythroid lineage progenitors, which upon transformation generate the bi-lineage leukemia-initiating cell. These results identify C/EBPa and GATA-2 ZnF1 mutations as causative of AEL, and demonstrate that transcriptional reprogramming by a leukemia-initiating mutation can re-define the lineage output of the resulting leukemia-initiating cells.
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| Overall design |
RNA-sequencing of bulk CD45.2+LKFcgRII/III+CD55-, CD45.1-EGFP-CD71hiTer119-/locKit+, and CD45.2+Mac1+cKitlo BM cells from three different competitively transplants recipients at pre-leukemic stage and corresponding leukemic populations in WT, Gata2G320D+ (G), CebpaK313KK/Lp30 (KL), and CebpaK313KK/Lp30;Gata2G320D/+ (KLG) mice
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| Contributor(s) |
Di Genua C, Nerlov C |
| Citation(s) |
32330454 |
| |
| Submission date |
Oct 18, 2018 |
| Last update date |
May 19, 2020 |
| Contact name |
Cristina Di Genua |
| E-mail(s) |
cristina.digenua@ndcls.ox.ac.uk
|
| Organization name |
University of Oxford
|
| Department |
Weatherall Institute of Molecular Medicine
|
| Street address |
Headley Way
|
| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (56)
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| This SubSeries is part of SuperSeries: |
| GSE141813 |
Combined mutation of C/EBPa and GATA-2 induce bi-lineage acute erythroid leukemia through transformation of a neomorphic neutrophil-erythroid progenitor |
|
| Relations |
| BioProject |
PRJNA497459 |
| SRA |
SRP166121 |
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