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Mendeley readers
Attention Score in Context
| Title |
Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL
|
|---|---|
| Published in |
Journal of Hematology & Oncology, September 2016
|
| DOI | 10.1186/s13045-016-0324-8 |
| Pubmed ID | |
| Authors |
L. Fransecky, M. Neumann, S. Heesch, C. Schlee, J. Ortiz-Tanchez, S. Heller, M. Mossner, S. Schwartz, L. H. Mochmann, K. Isaakidis, L. Bastian, U. R. Kees, T. Herold, K. Spiekermann, N. Gökbuget, C. D. Baldus |
| Abstract |
GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium® HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3(low) and GATA3(high) expressing T-ALL patients. In addition, the ETP-ALL cell line PER-117 was investigated for cytotoxicity, apoptosis, GATA3 mRNA expression, DNA methylation, and global gene expression before and after treatment with decitabine. In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3(low). DNA methylation analysis revealed a high degree of GATA3 CpG island methylation in GATA3(low) compared with GATA3(high) ETP-ALL patients (mean 46 vs. 21 %, p < 0.0001). Genome-wide expression profiling of GATA3(low) ETP-ALL exhibited enrichment of myeloid/lymphoid progenitor (MLP) and granulocyte/monocyte progenitor (GMP) genes, while T cell-specific signatures were downregulated compared to GATA3(high) ETP-ALL. Among others, FLT3 expression was upregulated and mutational analyses demonstrated a high rate (79 %) of FLT3 mutations. Hypomethylating agents induced reversal of GATA3 silencing, and gene expression profiling revealed downregulation of hematopoietic stem cell genes and upregulation of T cell differentiation. We propose GATA3(low) ETP-ALL as a novel stem cell-like leukemia with implications for the use of myeloid-derived therapies. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 33 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 27% |
| Student > Ph. D. Student | 5 | 15% |
| Student > Doctoral Student | 4 | 12% |
| Student > Bachelor | 2 | 6% |
| Student > Master | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 8 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 27% |
| Medicine and Dentistry | 9 | 27% |
| Immunology and Microbiology | 4 | 12% |
| Agricultural and Biological Sciences | 2 | 6% |
| Nursing and Health Professions | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 7 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 September 2016.
All research outputs
#15,384,989
of 22,889,074 outputs
Outputs from Journal of Hematology & Oncology
#778
of 1,192 outputs
Outputs of similar age
#202,956
of 321,009 outputs
Outputs of similar age from Journal of Hematology & Oncology
#16
of 25 outputs
Altmetric has tracked 22,889,074 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,192 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.8. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 321,009 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 25 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.