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Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
We report here an improved protocol to reprogram mouse gallbladder cells (GBCs) into pancreatic beta cells. To fully understand the extent of reprogramming, mRNA was extracted from FACS-purified MIP-GFP positive insulin-producing cells (namely rGBC2) for RNA-seq after 10-days of in vitro reprogramming. The global gene expression profile of rGBC2 was compared with that of primary gallbladder cells, GBC reprogrammed with the rGBC1 protocol (Hickey et al., 2013) and mouse pancreatic ß cells (Benner et al., 2014). We show that rGBC2 from four independent cell batches showed a unique gene expression phenotype. Compared with the rGBC1 protocol, rGBC2 expressed many additional pancreatic ß cell genes, suppressed many gallbladder genes and resulted in an expression profile closer to pancreatic ß cells. Overall design: Gene expression profiling of galbladder reprogrammed, insulin positive cells using the improved reprogramming protocol
Publication Title
Efficient generation of pancreatic β-like cells from the mouse gallbladder.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The clinical impact of aberrant CEBPA promoter methylation (PM) in AML is controversial discussed. The aim of this study was to clarify the significance of aberrant CEBPA PM with regard to clinical features in a cohort of 572 de novo AML with wildtype CEBPA and normal karyotype. The distal promoter was methylated in 54/572 cases (9.41%) whereas proximal PM was never detected. Methylation of the core promoter was detected in only 8 of 326 cases (2.45%) and thus seems to be a rare event in AML. There was no correlation between CEBPA distal PM, age, sex, white blood cell (WBC) count or Hb levels at diagnosis. We also were not able to detect a significant correlation between the presence of CEBPA distal PM and molecular mutations such as FLT3-ITD, NPM1, AML1, MLL-PTD and IDH1. Solely the frequency of IDH2R140 mutations was significantly reduced in CEBPA distal PM positive compared to CEBPA distal PM negative cases (p=0.01). Furthermore, analysis of CEBPA mRNA expression level revealed no difference between CEBPA distal PM positive and CEBPA distal PM negative cases, suggesting that CEBPA distal PM has no influence on CEBPA expression. CEBPA distal PM did not show impact on overall survival (OS), event free survival (EFS) or incidence of relapse. Also when other mutations were taken into regard no prognostic impact of CEBPA distal PM could be shown. In contrast, a distinct expression profile of CEBPA distal PM positive cases compared to CEBPA mutated and CEBPA distal PM negative cases was observed. In addition, a significantly higher frequency of CEBPA distal PM was detected in RUNX1-RUNX1T1 positive AML compared to the CEBPA witdtype cases. We conclude that the presence of aberrant CEBPA PM has no clinical relevance and is therefore a negligible prognostic marker in de novo AML with normal karyotype.
Publication Title
Frequency and prognostic impact of CEBPA proximal, distal and core promoter methylation in normal karyotype AML: a study on 623 cases.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 85 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as AML not otherwise specified or AML with myelodysplasia-related changes
Publication Title
Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as "AML not otherwise specified" (AML-NOS) or "AML with myelodysplasia-related changes" (AML-MRC).
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
By WHO 2008, CEBPA-mutated AML became a provisional subentity, but it remains to be clarified how CEBPAmut AML with multilineage dysplasia (MLD; 50% dysplastic cells in 2-3 lineages) but no other MDS-related feature should be classified. We investigated 108 CEBPAmut AML (15.7-87.6 years) for the impact of MLD and genetic features. MLD-positive patients differed from MLD-negative only by lower mean WBC counts (p=0.004), but not by other blood values, biologic characteristics, cytogenetic risk profiles, or additional molecular markers (NPM1mut, FLT3-ITD/TKD, RUNX1, MLL-PTD, IDH1/2). Biallelic CEBPAmut differed from wild-type-cases by differential expression of 213 genes, but did not differ significantly between MLD-positive/-negative patients. Survival outcomes were improved for females and those <60 years, intermediate versus adverse karyotypes (p=0.021), and for biallelic versus monoallelic/homozygous CEBPAmut (p=0.060) in case of FLT3-ITD-negativity. In contrast, 2-year OS (MLD+: 56.5%; MLD-: 65.5%) and 2-year EFS (MLD+: 13.8 months; MLD-: 16.3 months) did not differ significantly between MLD-positive/-negative patients. By univariable Cox regression analysis, gender, age, WBC count and MRC-cytogenetic risk category only were prognostically relevant for OS, while MLD was irrelevant. Therefore, CEBPAmut AML patients should be characterized only according to mut-status, cytogenetic risk groups, or additional mutations, whereas dysplasia is not relevant for this subtype.
Publication Title
Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interest focuses on genes encoding histone demethylases in hematologic malignancies, such as EZH2 (enhancer of zeste homolog 2). EZH2 mutations were recurrently observed in lymphomas and chronic myeloid malignancies, but data in acute leukemias are limited. We investigated 13 PICALM-MLLT10 (=CALM-AF10) rearranged acute leukemia predominantly of T-lineage (7 m/6 f; 653 years) by deep-sequencing for EZH2mut and identified 3 (23%) EZH2mut carriers: one splice site mutation in exon 14, while two patients had missense mutations in the D1 region of exon 5 which interacts with different DNA methyltransferase genes (but no DNMT3Amut was detected in the 13 PICALM-MLLT10-positive patients).
Publication Title
EZH2 mutations and their association with PICALM-MLLT10 positive acute leukaemia.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples
GSE10258- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a later onset, a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p and 7q, as well as fast progression of the disease with extremely poor prognosis. We and other have shown that the MLL gene is over expressed in amplified cases, however, in most of the cases the amplified region is not restricted to the MLL locus. In the present study we investigated 19 patients with AML/MDS and MLL gain/amplification [15 AML (two secondary, following MDS and PV, and three therapy related) and 4 MDS cases (two therapy related)]. By means of array CGH performed in 12 patients (GSE9928) we were able to delineate the minimal deleted regions within 5q, 17p and 7q and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases were used to define the candidate genes within these regions. Interestingly, analysis of our data suggests an interdependency of genes influenced by losses of 5q and 17p and expression of genes present in 11q23-25. Additionally, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from all other types of AML, thus, indicating specific pathogenesis present in this entity.
Publication Title
AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute myeloid leukemia (AML) with CEBPA mutations is determined as provisional entity in the current WHO. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon dm cases were shown to be associated with longer overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now. Here, we investigated a cohort of 95 AML CEBPAdm cases for concomitant mutations. TET2 was found to be the most frequent mutation (32/94, 34.0%), followed by GATA2 (20/95, 21.0%), WT1 (13/95, 13.7%), DNMT3A (9/94, 9.6%), ASXL1 (9/95, 9.5%), NRAS (8/95, 8.4%), KRAS (3/94, 3.2%), IDH1/2 (6/95, 6.3%), FLT3-ITD (6/95, 6.3%), FLT3-TKD (2/95, 2.1%), NPM1 (2/95, 2.1%), and RUNX1 (1/94). No mutation was detected in MLL-PTD and TP53. With respect to prognostic impact, we observed that those cases harboring additional mutations in TET2 showed significant worse survival than wild-type cases (P=0.035), whereas GATA2 mutated cases showed improved survival (P=0.032). Further, using gene expression microarray analysis we identified no clear different clustering within the CEBPAdm cases with the distinct concomitant mutated genes. In conclusion, we demonstrated that 76.8% of CEBPAdm cases harbored additional alterations in other molecular markers and that CEBPA is a suitable MRD marker to control therapy.
Publication Title
CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76·8% of cases with TET2 and GATA2 alterations impacting prognosis.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 106 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
AML with mutated NPM1 usually carries normal karyotype (NK) but it may harbor chromosomal aberrations whose significance remains unclear. We addressed this question in 631 AML patients with mutated/cytoplasmic NPM1. An abnormal karyotype (AK) was present in 93/631 cases (14.7%), the most frequent abnormalities being +8, +4, -Y, del(9q), +21. Chromosome aberrations in NPM1-mutated AML were similar to, but occurred less frequently than additional chromosome changes found in other AML with recurrent cytogenetic abnormalities according to WHO classification. Four of the 31 NPM1-mutated AML patients karyotyped at different time points had NK at diagnosis but AK at relapse: del(9q) (n=2), t(2;11) (n=1), inv(12) (n=1).
Publication Title
AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We compared gene expression profiles of Th cells, macrophages and monocytes isolated from the inflamed colon of colitis induced by the transfer of WT versus Tbx21-/- Th cells in Rag1-/- recipients.
Publication Title
T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The maintenance of the TFH phenotype depends on continuous signals via ICOS. For a global assessment of differences in gene expression after interruption of the ICOS pathway a genome wide transcriptome analysis was performed. We used the OT-II adoptive transfer system to isolate antigen-specific TFH cells (day 6 after immunization) after short-term (6 hours) blockade of the ICOS pathway using a monoclonal antibody against ICOS-L.
Publication Title
ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples