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Status |
Public on Jul 31, 2018 |
Title |
Expression of MLL-ENL in hematopoietic stem cells induces mixed lineage acute leukemia |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The t(11;19)(q23;p13.3) translocation leading to the expression of an MLL-ENL fusion is one of the most prevalent alterations affecting the mixed lineage leukemia 1 (MLL1) gene, mostly associated with B-cell acute lymphoblastic leukemia (ALL). Using a doxycycline (DOX)-inducible transgenic mouse model (“iMLL-ENL”) we show that direct induction or induction following transplantation of hematopoietic stem cells (HSC) but not of committed myeloid granulocyte-macrophage progenitors (GMP) leads to reversible acute mixed lineage leukemia. Disease induction was associated with iMLL-ENL levels exceeding the endogenous Mll1. iMLL-ENL leukemia was composed of small B220High cells with higher leukemia-initiating potential than co-existing larger-sized B220Low cells. Collectively, characterization of a novel transgenic mouse model indicates that the cell-of-origin and the expression levels above Mll1/MLL1 are both critical determinants for mixed lineage leukemia induced by the MLL-ENL fusion.
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Overall design |
RNA-sequencing of hematopoietic stem cells in control and iMLL-ENLleukemic mice (total bone marrow or sorted for HIGH and LOW expression levels of the surface marker B220)
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Contributor(s) |
Royo H, Stavropoulou V, Schwaller J, Peters AM |
Citation missing |
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Submission date |
Jul 29, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Antoine Peters |
E-mail(s) |
antoine.peters@fmi.ch
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Organization name |
Friedrich Miescher Institute for Biomedical Research (FMI)
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Street address |
Maulbeerstrasse 66
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City |
Basel |
ZIP/Postal code |
4058 |
Country |
Switzerland |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA335836 |
SRA |
SRP080322 |