Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA185474 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RET expression is upregulated in AML subtypes harboring genetic fusions of MLL-1 genes compared to age-matched healthy donors and other AML subtypes. In addition, we identify a novel epigenetic mechanism of RET overexpression in MLL-rearranged AML.
2024-03-04 | GSE241738 | GEO
Project description:FOXM1 Controls Leukemia Stem Cell Fate in MLL-Rearranged AML
| PRJNA515914 | ENA
Project description:Initiation of MLL-rearranged AML is orchestrated by C/EBPa
| PRJNA203263 | ENA
Project description:MLL-fusion proteins can induce acute myeloid leukemias (AML) from either hematopoietic stem cells (HSC) or granulocyte macrophage progenitors (GMP), but it remains unclear if the cell of origin influences the biology of the resultant leukemia. MLL-AF9 transduced single HSC or GMP could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate AML in mice. Leukemia stem cells derived from either HSC or GMP had a similar immunophenotype consistent with a maturing myeloid cell (LGMP). Gene expression analyses demonstrated that LGMP inherited gene expression programs from the cell of origin including high-level Evi-1 expression in HSC derived LGMP. The gene expression signature of LGMP derived from HSC was enriched in poor prognosis human MLL-rearranged AML in three independent data sets. Moreover, global 5’-mC levels were elevated in HSC-derived leukemias as compared to GMP-derived leukemias. This mirrored a difference seen in 5-mC between MLL-rearranged human leukemias that are either EVI1-positive or EVI1-negative. Finally, HSC derived leukemias were more resistant to chemotherapy than GMP-derived leukemias. These data demonstrate that the cell of origin influences the gene expression profile, the epigenetic state, and the drug response in AML, and that these differences can account for clinical heterogeneity within a molecularly defined group of leukemias. Differential DNA methylation between of LSC isolated from murine HSC and GMP derived AMLs
2013-01-09 | E-GEOD-43333 | biostudies-arrayexpress
Project description:Acute Myeloid Leukemia (AML) with MLL gene rearrangements demonstrate unique gene expression profiles driven by MLL-fusion proteins. Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL rearranged AMLs. SHARP1 is expressed solely in MLL-AF6 AML, and its expression is regulated directly by MLL-AF6 / DOT1L. Suppression of SHARP1 induces robust apoptosis of human MLL-AF6 AML cells. Genetic deletion in mice delays the development of leukemia and attenuated leukemia-initiating potential, while sparing normal hematopoiesis. Mechanistically, SHARP1 binds to transcriptionally active chromatin across the genome and activates genes critical for cell survival as well as key oncogenic targets of MLL-AF6. Our findings demonstrate the unique oncogenic role for SHARP1 in MLL-AF6 AML.
2018-04-26 | GSE95511 | GEO
Project description:MLL-fusion proteins can induce acute myeloid leukemias (AML) from either hematopoietic stem cells (HSC) or granulocyte macrophage progenitors (GMP), but it remains unclear if the cell of origin influences the biology of the resultant leukemia. MLL-AF9 transduced single HSC or GMP could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate AML in mice. Leukemia stem cells derived from either HSC or GMP had a similar immunophenotype consistent with a maturing myeloid cell (LGMP). Gene expression analyses demonstrated that LGMP inherited gene expression programs from the cell of origin including high-level Evi-1 expression in HSC derived LGMP. The gene expression signature of LGMP derived from HSC was enriched in poor prognosis human MLL-rearranged AML in three independent data sets. Moreover, global 5’-mC levels were elevated in HSC-derived leukemias as compared to GMP-derived leukemias. This mirrored a difference seen in 5-mC between MLL-rearranged human leukemias that are either EVI1-positive or EVI1-negative. Finally, HSC derived leukemias were more resistant to chemotherapy than GMP-derived leukemias. These data demonstrate that the cell of origin influences the gene expression profile, the epigenetic state, and the drug response in AML, and that these differences can account for clinical heterogeneity within a molecularly defined group of leukemias.
2013-01-09 | GSE43333 | GEO
Project description:ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. In this study, we show that ZNF521 is significantly upregulated in MLL translocated AML patients from a large pediatric cohort, regardless of the type of MLL translocations such as MLL-AF9, MLL-ENL, MLL-AF10 and MLL-AF6 fusion genes. Our in vitro functional studies demonstrate that ZNF521 play a critical role in the maintenance of the undifferentiated state of MLL-rearranged cells. Furthermore, analysis of the ZNF521 gene promoter region shows that ZNF521 is a direct downstream target of both MLL-AF9 and MLL-ENL fusion proteins. Gene expression profiling of MLL-AF9-rearranged THP-1 cells after depletion of ZNF521 reveals correlation with several expression signatures including stem cell-like and MLL fusion dependent programs. These data suggest that MLL fusion proteins activate ZNF521 expression to maintain the undifferentiated state and contribute to leukemogenesis. ZNF521 is required to block differentiation in MLL-rearranged AML cells
2017-03-31 | GSE79110 | GEO
Project description:MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling of human AML and normal control samples, we found that ALOX5 is especially down-regulated in MLL-rearranged AML. Our colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo. Strikingly, leukemic cells with Alox5 overexpression showed a significantly higher sensitivity to the standard chemotherapeutic agents, i.e., doxorubicin (DOX) and cytarabine (Ara-C). The drug-sensitizing role of Alox5 was further confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as in the in vivo MLL-rearranged AML BMT model coupled with treatment of “5+3” (i.e. DOX plus Ara-C) regimen. Our RNA-seq analysis showed that Stat and K-Ras signaling pathways were negatively correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells, implying targeting those pathways likely contributes to Alox5’s functions. Collectively, our work shows that ALOX5 plays a moderate anti-tumor role and functions as a drug sensitizer, with a therapeutic potential, in MLL-rearranged AML.
2017-06-09 | GSE94840 | GEO
Project description:Acute myeloid leukemia (AML) carrying MLL rearrangements. We applied WGBS and the informME analysis pipeline to investigate the role of DNA methylation stochasticity in MLL-rearranged AML.
2020-03-02 | GSE135869 | GEO
Project description:Leukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biological characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes including HOXA9. Here, we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias utilizing RNAi. Gene expression profiling after HOXA9 suppression demonstrated co-downregulation of a program highly expressed in human MLL-AML (this study) and murine MLL-leukemia (Krivtsov et al. 2006) stem cells including HOXA10, MEIS1, PBX3 and MEF2C. Our data indicates an important role for HOXA9 in human MLL-rearranged leukemias, and suggests targeting HOXA9 or downstream programs may be a novel therapeutic option. Experiment Overall Design: RNA was purified from t(9;11) MOLM-14 AML cells 44h after transduction in triplicates with 2 of the two most effective HOXA9shRNA constructs (3 x 1F3-HOXA9shRNA; 3 x 2A5-HOXA9shRNA) or GFP-controlshRNA (6x).
2009-01-26 | E-GEOD-13714 | biostudies-arrayexpress